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Version: 3.16

Nirvana JSON File Format

Overview

Conventions

In the Nirvana JSON representation, we try to maximize the amount of useful information that is relayed in the output file. As such, we have several conventions that are useful to know about:

  • With boolean key/value pairs, we only output the keys that have a true value. I.e. there's no reason to display "isStructuralVariant":false a few million times when annotating a small variant VCF.
  • When transferring data from the VCF file to the JSON (e.g. for allele depths (AD)), it is common to use a period (.) as a placeholder for missing data in the VCF file. Nirvana treats periods like empty or null strings and therefore will not output those entries.

JSON Layout

info

In general, each position corresponds to a row in the original VCF file.

For each gene that was referenced in the transcripts found in the positions section, there will be additional gene-level annotation in the gene section.

Parsing

info

We've put together a new section that discusses how to parse our JSON files easily using examples in a Python Jupyter notebook and a R version as well. In addition, we have information about how to quickly dump content from our JSON file using a tabix-like utility called JASIX.

{
"header":{
"annotator":"Nirvana 3.0.0-alpha.5+g6c52e247",
"creationTime":"2017-06-14 15:53:13",
"genomeAssembly":"GRCh37",
"dataSources":[
{
"name":"OMIM",
"version":"unknown",
"description":"An Online Catalog of Human Genes and Genetic Disorders",
"releaseDate":"2017-05-03"
},
{
"name":"VEP",
"version":"84",
"description":"BothRefSeqAndEnsembl",
"releaseDate":"2017-01-16"
},
{
"name":"ClinVar",
"version":"20170503",
"description":"A freely accessible, public archive of reports of the relationships among human variations and phenotypes, with supporting evidence",
"releaseDate":"2017-05-03"
},
{
"name":"phyloP",
"version":"hg19",
"description":"46 way conservation score between humans and 45 other vertebrates",
"releaseDate":"2009-11-10"
}
],
"samples":[
"NA12878",
"NA12891",
"NA12892"
]
},
FieldTypeNotes
annotatorstringthe name of the annotator and the current version
creationTimestringyyyy-MM-dd hh:mm:ss
genomeAssemblystringsee possible values below
schemaVersionintegerincremented whenever the core structure of the JSON file introduces breaking changes
dataVersionstring
dataSourcesobject arraysee Data Source entry below
samplesstring arraythe order of these sample names will be used throughout the JSON file when enumerating samples

Data Source

FieldTypeNotes
namestring
versionstring
descriptionstringoptional description of the data source
releaseDatestringyyyy-MM-dd

Genome Assemblies

  • GRCh37
  • GRCh38
  • hg19
  • SARSCoV2

Positions

"positions":[
{
"chromosome":"chr2",
"position":48010488,
"repeatUnit":"GGCCCC",
"refRepeatCount":3,
"svEnd":48020488,
"refAllele":"G",
"altAlleles":[
"A",
"GT"
],
"quality":461,
"filters":[
"PASS"
],
"ciPos":[
-170,
170
],
"ciEnd":[
-175,
175
],
"svLength":1000,
"strandBias":1.23,
"jointSomaticNormalQuality":29,
"cytogeneticBand":"2p16.3",
FieldTypeVariant TypeNotes
chromosomestringallexactly as displayed in the vcf
positionintegerallexactly as displayed in the vcf (1-based notation). Range: 1 - 250 million
repeatUnitstringSTRprovided by ExpansionHunter
refRepeatCountintegerSTRprovided by ExpansionHunter
svEndintegerSV
refAllelestringallexactly as displayed in the vcf
altAllelestring arrayallexactly as displayed in the vcf
qualityfloatallexactly as displayed in the vcf (Normally an integer, but some variant callers using floating point. Has been observed as high as 500k)
filtersstring arrayallexactly as displayed in the vcf
ciPosinteger arraySV
ciEndinteger arraySV
svLengthintegerSV
strandBiasfloatsmall variantprovided by GATK (from SB)
jointSomaticNormalQualityintegerSVprovided by the Manta variant caller (SOMATICSCORE)
cytogeneticBandstringalle.g. 17p13.1

ClinGen

"clingen":[
{
"chromosome":"17",
"begin":525,
"end":14667519,
"variantType":"copy_number_gain",
"id":"nsv996083",
"clinicalInterpretation":"pathogenic",
"observedGains":1,
"validated":true,
"phenotypes":[
"Intrauterine growth retardation"
],
"phenotypeIds":[
"HP:0001511",
"MedGen:C1853481"
],
"reciprocalOverlap":0.00131
},
{
"chromosome":"17",
"begin":45835,
"end":7600330,
"variantType":"copy_number_loss",
"id":"nsv869419",
"clinicalInterpretation":"pathogenic",
"observedLosses":1,
"validated":true,
"phenotypes":[
"Developmental delay AND/OR other significant developmental or morphological phenotypes"
],
"reciprocalOverlap":0.00254
}
]
FieldTypeNotes
clingenobject array
chromosomestringEnsembl-style chromosome names
begininteger1-based position
endinteger1-based position
variantTypestringAny of the sequence alterations defined here.
idstringIdentifier from the data source. Alternatively a VID
clinicalInterpretationstringsee possible values below
observedGainsintegerRange: 0 - (231 - 1). Only used if copy_number_variation, copy_number_loss, or copy_number_gain.
observedLossesintegerRange: 0 - (231 - 1). Only used if copy_number_variation, copy_number_loss, or copy_number_gain.
validatedboolean
phenotypesstring arrayDescription of the phenotype.
phenotypeIdsstring arrayDescription of the phenotype IDs.
reciprocalOverlapfloating pointRange: 0 - 1. E.g. 0.57 would indicate a 57% reciprocal overlap. Specified up to 5 decimal places (Not reported for Insertions).

clinicalInterpretation

  • benign
  • curated benign
  • curated pathogenic
  • likely benign
  • likely pathogenic
  • path gain
  • path loss
  • pathogenic
  • uncertain
"clingenDosageSensitivityMap": [{
"chromosome": "15",
"begin": 30900686,
"end": 32153204,
"haploinsufficiency": "sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype",
"triplosensitivity": "little evidence suggesting dosage sensitivity is associated with clinical phenotype",
"reciprocalOverlap": 0.00147,
"annotationOverlap": 0.33994
},
{
"chromosome": "15",
"begin": 31727418,
"end": 32153204,
"haploinsufficiency": "sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype",
"triplosensitivity": "dosage sensitivity unlikely",
"reciprocalOverlap": 0.00147,
"annotationOverlap": 1
}]
FieldTypeNotes
clingenDosageSensitivityMapobject array
chromosomestringEnsembl-style chromosome names
begininteger1-based position
endinteger1-based position
haploinsufficiencystringsee possible values below
triplosensitivitystring(same as haploinsufficiency) 
reciprocalOverlapfloating pointRange: 0 - 1. E.g. 0.57 would indicate a 57% reciprocal overlap. Specified up to 5 decimal places (Not reported for Insertions).
annotationOverlapfloating pointRange: 0 - 1. E.g. 0.57 would indicate a 57% reciprocal overlap. Specified up to 5 decimal places (Not reported for Insertions).

haploinsufficiency and triplosensitivity

  • no evidence to suggest that dosage sensitivity is associated with clinical phenotype
  • little evidence suggesting dosage sensitivity is associated with clinical phenotype
  • emerging evidence suggesting dosage sensitivity is associated with clinical phenotype
  • sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype
  • gene associated with autosomal recessive phenotype
  • dosage sensitivity unlikely

1000 Genomes (SV)

"oneKg":[
{
"chromosome":"1",
"begin":1595369,
"end":1612441,
"variantType": "copy_number_variation",
"id": "esv3635753;esv3635754;esv3635755;esv3635756;esv3635757",
"allAn": 5008,
"allAc": 2702,
"allAf": 0.539537,
"afrAf": 0.6052,
"amrAf": 0.3675,
"eurAf": 0.5357,
"easAf": 0.5368,
"sasAf": 0.5797,
"reciprocalOverlap": 0.07555
}
],
FieldTypeNotes
chromosomestring
begininteger
endinteger
variantTypestring
idstring
allAnfloating pointallele number for all populations. Non-zero integer.
allAcfloating pointallele count for all populations. Integer.
allAffloating pointallele frequency for all populations. Range: 0 - 1.0
afrAffloating pointallele frequency for the African super population. Range: 0 - 1.0
amrAffloating pointallele frequency for the Ad Mixed American super population. Range: 0 - 1.0
eurAffloating pointallele frequency for the European super population. Range: 0 - 1.0
easAfintegerallele frequency for the East Asian super population. Range: 0 - 1.0
sasAfintegerallele frequency for the South Asian super population. Range: 0 - 1.0
reciprocalOverlapfloating pointrange: 0 - 1.

MITOMAP (SV)

"mitomap":[ 
{
"chromosome":"MT",
"begin":3166,
"end":14152,
"variantType":"deletion",
"reciprocalOverlap":0.18068,
"annotationOverlap":0.42405
}
]
FieldTypeNotes
chromosomestring
begininteger
endinteger
variantTypestring array
reciprocalOverlapfloatRange: 0 - 1. Specified up to 5 decimal places
annotationOverlapfloatRange: 0 - 1. Specified up to 5 decimal places

Samples

"samples":[
{
"genotype":"0/1",
"variantFrequencies":[
0.333,
0.5
],
"totalDepth":57,
"genotypeQuality":12,
"copyNumber":3,
"repeatUnitCounts":[
10,
20
],
"alleleDepths":[
10,
20,
30
],
"failedFilter":true,
"splitReadCounts":[
10,
20
],
"pairedEndReadCounts":[
10,
20
],
"isDeNovo":true,
"diseaseAffectedStatuses":[
"-"
],
"artifactAdjustedQualityScore":89.3,
"likelihoodRatioQualityScore":78.2,
"heteroplasmyPercentile":[
23.13,
12.65
]
}
]
FieldTypeNotes
genotypestring
variantFrequenciesfloat arrayrange: 0 - 1.0. One value per alternate allele
totalDepthintegernon-negative integer values
genotypeQualityintegernon-negative integer values. Typically maxes out at 99
copyNumberintegernon-negative integer values
repeatUnitCountsinteger arrayExpansionHunter-specific
alleleDepthsinteger arraynon-negative integer values
failedFilterbool
splitReadCountsinteger arrayManta-specific
pairedEndReadCountsinteger arrayManta-specific
isDeNovobool
diseaseAffectedStatusesstring arrayExpansionHunter-specific
artifactAdjustedQualityScorefloatPEPE-specific. Range: 0 - 100.0
likelihoodRatioQualityScorefloatPEPE-specific. Range: 0 - 100.0
heteroplasmyPercentilefloatrange: 0 - 100. 2 decimal places. One value per alternate allele
Empty Samples

If a sample does not contain any entries, we will create a sample object that contains the isEmpty key. This ensures that sample ordering is preserved while indicating that a sample is intentionally empty.

"samples":[
{
"isEmpty":true
}
],

Variants

"variants":[
{
"vid":"2:48010488:A",
"chromosome":"chr2",
"begin":48010488,
"end":48010488,
"isReferenceMinorAllele":true,
"isStructuralVariant":true,
"refAllele":"G",
"altAllele":"A",
"variantType":"SNV",
"isDecomposedVariant":true,
"isRecomposedVariant":true,
"linkedVids":["2:48010488:GTA:ATC"],
"hgvsg":"NC_000002.11:g.48010488G>A",
"phylopScore":0.459
FieldTypeNotes
vidstringsee Variant Identifiers
chromosomestring
beginint1-based non-negative integer values. Range: 1 - 250 million
endint1-based non-negative integer values. Range: 1 - 250 million
isReferenceMinorAllelebooltrue when this is a reference minor allele
isStructuralVariantbooltrue when the variant is a structural variant
inLowComplexityRegionbooltrue when the variant lies in a low complexity region (gnomAD low complexity regions)
refAllelestringparsimonious representation of the reference allele
altAllelestringparsimonious representation of the alternate allele.
variantTypestringuses Sequence Ontology sequence alterations
isDecomposedVariantbooltrue when the decomposed variant has been used to create another recomposed variant
isRecomposedVariantbooltrue when the variant is recomposed from two or more decomposed variants
linkedVidsstring arraylist of VIDs for variants connecting decomposed and recomposed variants
hgvsgstringHGVS g. notation
phylopScorefloatphyloP conservation score. Range: -14.08 to 6.424
Reference Minor Alleles

Nirvana supports annotating reference minor alleles. In such a case, refAllele will be replaced by the global major allele and altAllele will be replaced with the original reference allele.

Flagging Decomposed & Recomposed Variants

When two or more decomposed variants are recomposed into an MNV, the decomposed variants will be marked with "isDecomposedVariant":true.

Similarly, the recomposed variant will be shown as a new VCF position. This recomposed variant will be flagged with "isRecomposedVariant":true.

Transcripts

"transcripts":[
{
"transcript":"ENST00000445503.1",
"source":"Ensembl",
"bioType":"nonsense_mediated_decay",
"codons":"gGg/gAg",
"aminoAcids":"G/E",
"cdnaPos":"268",
"cdsPos":"116",
"exons":"1/9",
"introns":"1/8",
"proteinPos":"39",
"geneId":"ENSG00000116062",
"hgnc":"MSH6",
"consequence":[
"missense_variant",
"NMD_transcript_variant"
],
"hgvsc":"ENST00000445503.1:c.116G>A",
"hgvsp":"ENSP00000405294.1:p.(Gly39Glu)",
"geneFusion":{
"exon":6,
"intron":5,
"fusions":[
{
"hgvsc":"ETV6{ENST00000396373.4}:c.1_1009+3402_RUNX1{ENST00000437180.1}:c.58+568_1443",
"exon":3,
"intron":2
},
{
"hgvsc":"ETV6{ENST00000396373.4}:c.1_1009+3402_RUNX1{ENST00000300305.3}:c.58+568_1443",
"exon":2,
"intron":1
}
]
},
"isCanonical":true,
"polyPhenScore":0.95,
"polyPhenPrediction":"probably damaging",
"proteinId":"ENSP00000405294.1",
"siftScore":0.61,
"siftPrediction":"tolerated",
"completeOverlap":true
}
]
FieldTypeNotes
transcriptstringtranscript ID. e.g. ENST00000445503.1
sourcestringRefSeq / Ensembl
bioTypestringdescriptions of the biotypes from Ensembl
codonsstring
aminoAcidsstring
cdnaPosstring
cdsPosstring
exonsstringexons affected by the variant
intronsstringintrons affected by the variant
proteinPosstring
geneIdstringgene ID. e.g. ENSG00000116062
hgncstringgene symbol. e.g. MSH6
consequencestring arraySequence Ontology Consequences
hgvscstringHGVS coding nomenclature
hgvspstringHGVS protein nomenclature
geneFusionobjectsee Gene Fusions entry below
isCanonicalbooltrue when this is a canonical transcript
polyPhenScorefloatrange: 0 - 1.0
polyPhenPredictionstringsee possible values below
proteinIdstringprotein ID. E.g. ENSP00000405294.1
siftScorefloatrange: 0 - 1.0
siftPredictionstringsee possible values below
completeOverlapbooltrue when this transcript is completely overlapped by the variant

PolyPhen

  • probably damaging
  • possibly damaging
  • benign
  • unknown

SIFT

  • tolerated
  • deleterious
  • tolerated - low confidence
  • deleterious - low confidence

Amino Acid Conservation

"aminoAcidConservation": {
"scores": [0.34]
}
FieldTypeNotes
aminoAcidConservationobject
scoresobject array of doublespercent conserved with respect to human amino acid residue. Range: 0.01 - 1.00

Gene Fusions

FieldTypeNotes
exonintactual exon where the breakpoint was located
intronintactual intron where the breakpoint was located
fusionsobject arraysee Fusion entry below

Fusion

FieldTypeNotes
exonintactual exon where the other breakpoint was located
intronintactual intron where the other breakpoint was located
hgvscstringHGVS coding nomenclature describing the two genes and the transcripts that are fused along with

Regulatory Regions

"regulatoryRegions":[
{
"id":"ENSR00001542175",
"type":"promoter",
"consequence":[
"regulatory_region_variant"
]
}
]
FieldTypeNotes
idstring
typestringsee possible values below
consequencestring arraysee possible values below

Regulatory Types

  • CTCF_binding_site
  • enhancer
  • open_chromatin_region
  • promoter
  • promoter_flanking_region
  • TF_binding_site

Regulatory Consequences

  • regulatory_region_variant
  • regulatory_region_ablation
  • regulatory_region_amplification
  • regulatory_region_truncation

ClinVar

"clinvar":[
{
"id":"VCV000036581.3",
"reviewStatus":"reviewed by expert panel",
"significance":[
"benign"
],
"refAllele":"G",
"altAllele":"A",
"lastUpdatedDate":"2020-03-01",
"isAlleleSpecific":true
},
{
"id":"RCV000030258.4",
"variationId":"VCV000036581.3",
"reviewStatus":"reviewed by expert panel",
"alleleOrigins":[
"germline"
],
"refAllele":"G",
"altAllele":"A",
"phenotypes":[
"Lynch syndrome"
],
"medGenIds":[
"C1333990"
],
"omimIds":[
"120435"
],
"significance":[
"benign"
],
"lastUpdatedDate":"2017-05-01",
"isAlleleSpecific":true
}
]
FieldTypeNotes
idstringClinVar ID
variationIdstringClinVar VCV ID
reviewStatusstringsee possible values below
alleleOriginsstring arraysee possible values below
refAllelestring
altAllelestring
phenotypesstring array
medGenIdsstring arrayMedGen IDs
omimIdsstring arrayOMIM IDs
orphanetIdsstring arrayOrphanet IDs
significancestring arraysee possible values below
lastUpdatedDatestringyyyy-MM-dd
pubMedIdsstring arrayPubMed IDs
isAlleleSpecificbooltrue when the current variant alternate allele matches the ClinVar alternate allele

reviewStatus:

  • no assertion provided
  • no assertion criteria provided
  • criteria provided, single submitter
  • practice guideline
  • classified by multiple submitters
  • criteria provided, conflicting interpretations
  • criteria provided, multiple submitters, no conflicts
  • no interpretation for the single variant

alleleOrigins:

  • unknown
  • other
  • germline
  • somatic
  • inherited
  • paternal
  • maternal
  • de-novo
  • biparental
  • uniparental
  • not-tested
  • tested-inconclusive

significance:

  • uncertain significance
  • not provided
  • benign
  • likely benign
  • likely pathogenic
  • pathogenic
  • drug response
  • histocompatibility
  • association
  • risk factor
  • protective
  • affects
  • conflicting data from submitters
  • other
  • no interpretation for the single variant
  • conflicting interpretations of pathogenicity

1000 Genomes

"oneKg":{
"allAf":0.200879,
"afrAf":0.210287,
"amrAf":0.139769,
"easAf":0.275794,
"eurAf":0.181909,
"sasAf":0.173824,
"allAn":5008,
"afrAn":1322,
"amrAn":694,
"easAn":1008,
"eurAn":1006,
"sasAn":978,
"allAc":1006,
"afrAc":278,
"amrAc":97,
"easAc":278,
"eurAc":183,
"sasAc":170
}
FieldTypeNotes
allAffloatallele frequency for all populations. Range: 0 - 1.0
allAcintallele count for all populations. Integer.
allAnintallele number for all populations. Non-zero integer.
afrAffloatallele frequency for the African super population. Range: 0 - 1.0
afrAcintallele count for the African super population. Integer.
afrAnintallele number for the African super population. Non-zero integer.
amrAffloatallele frequency for the Ad Mixed American super population. Range: 0 - 1.0
amrAcintallele count for the Ad Mixed American super population. Integer.
amrAnintallele number for the Ad Mixed American super population. Non-zero integer.
easAffloatallele frequency for the East Asian super population. Range: 0 - 1.0
easAcintallele count for the East Asian super population. Integer.
easAnintallele number for the East Asian super population. Non-zero integer.
eurAffloatallele frequency for the European super population. Range: 0 - 1.0
eurAcintallele count for the European super population. Integer.
eurAnintallele number for the European super population. Non-zero integer.
sasAffloatallele frequency for the South Asian super population. Range: 0 - 1.0
sasAcintallele count for the South Asian super population. Integer.
sasAnintallele number for the South Asian super population. Non-zero integer.

gnomAD

"gnomad":{ 
"coverage":20,
"allAf":0.190317,
"maleAf":0.193,
"femaleAf": 0.1935,
"afrAf":0.222876,
"amrAf":0.121394,
"easAf":0.239802,
"finAf":0.136833,
"nfeAf":0.181282,
"asjAf":0.258278,
"othAf":0.186094,
"allAn":30796,
"maleAn":15096,
"femaleAn":15700
"afrAn":8664,
"amrAn":832,
"easAn":1618,
"finAn":3486,
"nfeAn":14916,
"asjAn":302,
"othAn":978,
"allAc":5861,
"maleAc":2930,
"femaleAc": 2931,
"afrAc":1931,
"amrAc":101,
"easAc":388,
"finAc":477,
"nfeAc":2704,
"asjAc":78,
"othAc":182,
"allHc":561,
"afrHc":208,
"amrHc":6,
"easHc":42,
"finHc":31,
"nfeHc":242,
"asjHc":13,
"othHc":19,
"maleHc":280,
"femaleHc":281,
"controlsAllAf":0.190317,
"controlsAllAn":30796,
"controlsAllAc":5861,
"lowComplexityRegion":true,
"failedFilter":true
}
FieldTypeNotes
coverageintaverage coverage (non-negative integer values)
allAffloatallele frequency for all populations. Range: 0 - 1.0
maleAffloatallele frequency for male population. Range: 0 - 1.0
femaleAffloatallele frequency for female population. Range: 0 - 1.0
controlsAllAffloatallele frequency for the controls subset. Range: 0 - 1.0
allAcintallele count for all populations. Integer.
maleAcintallele count for male population. Integer.
femaleAcintallele count for female population. Integer.
controlsAllAcintallele count for the controls subset. Integer.
allAnintallele number for all populations. Non-zero integer.
maleAnintallele number for male population. Non-zero integer.
femaleAnintallele number for female population. Non-zero integer.
controlsAllAnintallele number for the controls subset. Non-zero integer.
allHcintcount of homozygous individuals for all populations. Non-negative integer.
maleHcintcount of homozygous individuals for male population. Non-negative integer.
femaleHcintcount of homozygous individuals for female population. Non-negative integer.
afrAffloatallele frequency for the African / African American population. Range: 0 - 1.0
afrAcintallele count for the African / African American population. Integer.
afrAnintallele number for the African / African American population. Non-zero integer.
afrHcintcount of homozygous individuals for African / African American population. Non-negative integer.
amrAffloatallele frequency for the Latino population. Range: 0 - 1.0
amrAcintallele count for the Latino population. Integer.
amrAnintallele number for the Latino population. Non-zero integer.
amrHcintcount of homozygous individuals for Latino population. Non-negative integer.
easAffloatallele frequency for the East Asian population. Range: 0 - 1.0
easAcintallele count for the East Asian population. Integer.
easAnintallele number for the East Asian population. Non-zero integer.
easHcintcount of homozygous individuals for East Asian population. Non-negative integer.
finAffloatallele frequency for the Finnish population. Range: 0 - 1.0
finAcintallele count for the Finnish population. Integer.
finAnintallele number for the Finnish population. Non-zero integer.
finHcintcount of homozygous individuals for Finnish population. Non-negative integer
nfeAffloatallele frequency for the Non-Finnish European population. Range: 0 - 1.0
nfeAcintallele count for the Non-Finnish European population. Integer.
nfeAnintallele number for the Non-Finnish European population. Non-zero integer.
nfeHcintcount of homozygous individuals for Non-Finnish European population. Non-negative integer
othAffloatallele frequency for the Other population. Range: 0 - 1.0
othAcintallele count for the Other population. Integer.
othAnintallele number for the Other population. Non-zero integer.
othHcintcount of homozygous individuals for Other population. Non-negative integer
asjAffloatallele frequency for the Ashkenazi Jewish population. Range: 0 - 1.0
asjAcintallele count for the Ashkenazi Jewish population Integer.
asjAnintallele number for the Ashkenazi Jewish population. Non-zero integer.
asjHcintcount of homozygous individuals for the Ashkenazi Jewish population. Non-negative integer
sasAffloatallele frequency for the South Asian population. Range: 0 - 1.0
sasAcintallele count for the South Asian population Integer.
sasAnintallele number for the South Asian population. Non-zero integer.
sasHcintcount of homozygous individuals for the South Asian population. Non-negative integer.
failedFilterboolTrue if this variant failed any filters (Note: we do not list the failed filters)
lowComplexityRegionboolTrue if this variant is located in a low complexity region.

dbSNP

"dbsnp":[
"rs1042821"
]
FieldTypeNotes
dbsnpstring arraydbSNP rsIDs

MITOMAP

"mitomap":[ 
{
"refAllele":"G",
"altAllele":"A",
"diseases":[
"Bipolar disorder",
"Melanoma"
],
"hasHomoplasmy":false,
"hasHeteroplasmy":true,
"status":"Reported",
"clinicalSignificance":"confirmed pathogenic",
"scorePercentile":83.30,
"numGenBankFullLengthSeqs":2,
"pubMedIds":["2316527","6299878","6301949"],
"isAlleleSpecific":true
}
]
FieldTypeNotes
refAllelestring
altAllelestring
diseasesstring arrayassociated diseases
hasHomoplasmyboolean
hasHeteroplasmyboolean
statusstringrecord status
clinicalSignificancestringpredicted pathogenicity
scorePercentilefloatMitoTIP score
numGenBankFullLengthSeqsinteger# of GenBank full-length sequences
pubMedIdsstring array
isAlleleSpecificbooleantrue when the current variant alternate allele matches the MITOMAP alternate allele

Primate AI

"primateAI":[
{
"hgnc":"TP53",
"scorePercentile":0.3,
}
]
FieldTypeNotes
hgncstring
scorePercentilefloatrange: 0 - 1.0

REVEL

"revel":{ 
"score":0.027
}
FieldTypeNotes
scorefloatRange: 0 - 1.0

Splice AI

"spliceAI":[ 
{
"hgnc":"BLCAP",
"acceptorGainDistance":-3,
"acceptorGainScore":0.3,
"donorLossDistance":7,
"donorLossScore":0.9
},
{
"hgnc":"NNAT",
"acceptorGainDistance":-1,
"acceptorGainScore":0.2,
"donorGainDistance":-2,
"donorGainScore":0.3
}
]
FieldTypeNotes
hgncstringHGNC gene symbol
acceptorGainDistanceint± bp from current position
acceptorGainScorefloatrange: 0 - 1.0. 1 decimal place
acceptorLossDistanceint± bp from current position
acceptorLossScorefloatrange: 0 - 1.0. 1 decimal place
donorGainDistanceint± bp from current position
donorGainScorefloatrange: 0 - 1.0. 1 decimal place
donorLossDistanceint± bp from current position
donorLossScorefloatrange: 0 - 1.0. 1 decimal place

TOPMed

"topmed":{ 
"allAc":20,
"allAn":125568,
"allAf":0.000159,
"allHc":0,
"failedFilter":true
}
FieldTypeNotes
allAcintTOPMed allele count
allAnintTOPMed allele number. Non-zero integer.
allAffloatTOPMed allele frequency (computed by Nirvana)
allHcintTOPMed homozygous count
failedFilterboolTrue if this variant failed any filters

Genes

"genes":[
{
"name":"MSH6",
"hgncId":7329,
"summary":"This gene encodes a member of the DNA mismatch repair MutS family. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein heterodimerizes with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene may be associated with hereditary nonpolyposis colon cancer, colorectal cancer, and endometrial cancer. Transcripts variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]",
/* this is where gene-level data sources can be found e.g. OMIM */
}
]
FieldTypeNotes
namestringHGNC gene symbol
hgncIdintHGNC ID
summarystringshort description of the gene from OMIM

OMIM

"omim":[ 
{
"mimNumber":600678,
"geneName":"MutS, E. coli, homolog of, 6",
"description":"The transcription factor p53 responds to diverse cellular stresses to regulate target genes that induce cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. In addition, p53 appears to induce apoptosis through nontranscriptional cytoplasmic processes. In unstressed cells, p53 is kept inactive essentially through the actions of the ubiquitin ligase MDM2, which inhibits p53 transcriptional activity and ubiquitinates p53 to promote its degradation. Numerous posttranslational modifications modulate p53 activity, most notably phosphorylation and acetylation. Several less abundant p53 isoforms also modulate p53 activity. Activity of p53 is ubiquitously lost in human cancer either by mutation of the p53 gene itself or by loss of cell signaling upstream or downstream of p53 (Toledo and Wahl, 2006; Bourdon, 2007; Vousden and Lane, 2007)",
"phenotypes":[
{
"mimNumber":614350,
"phenotype":"Colorectal cancer, hereditary nonpolyposis, type 5",
"description":"Hereditary nonpolyposis colorectal cancer type 5 is a cancer predisposition syndrome ...",
"mapping":"molecular basis of the disorder is known",
"inheritances":[
"Autosomal dominant"
]
},
{
"mimNumber":608089,
"phenotype":"Endometrial cancer, familial",
"mapping":"molecular basis of the disorder is known"
},
{
"mimNumber":276300,
"phenotype":"Mismatch repair cancer syndrome",
"description":"Constitutional mismatch repair deficiency is a rare childhood cancer predisposition syndrome ...",
"mapping":"molecular basis of the disorder is known",
"inheritances":[
"Autosomal recessive"
],
"comments" : [
"contribute to susceptibility to multifactorial disorders or to susceptibility to infection",
"unconfirmed or possibly spurious mapping"
]
}
]
}
]
FieldTypeNotes
mimNumberintOMIM ID for gene
geneNamestringgene name
descriptionstring
phenotypesobject arraysee Phenotype entry below

Phenotype

FieldTypeNotes
mimNumberint
phenotypestring
descriptionstring
mappingstringsee possible values below
inheritancestring arraysee possible values below
commentsstring arraysee possible values below

Mapping

  1. disorder was positioned by mapping of the wild type gene
  2. disease phenotype itself was mapped
  3. molecular basis of the disorder is known
  4. disorder is a chromosome deletion or duplication syndrome

Inheritance

  • autosomal recessive
  • autosomal dominant

Comments

  • contributes to the susceptibility to multifactorial disorders
  • variations that lead to apparently abnormal laboratory test values
  • unconfirmed mapping

gnomAD LoF Gene Metrics

"gnomAD":{ 
"pLi":1.00e0,
"pNull":8.94e-40,
"pRec":1.84e-16,
"synZ":-8.44e-2,
"misZ":5.96e-1,
"loeuf":1.13e0
}
FieldTypeNotes
pLifloatprobability of being intolerant of a single loss-of-function variant (like haploinsufficient genes, observed ~ 0.1*expected)
pNullfloatprobability of being completely tolerant of loss of function variation (observed = expected)
pRecfloatprobability of being intolerant of two loss of function variants (like recessive genes, observed ~ 0.5*expected)
synZfloatcorrected synonymous Z score
misZfloatcorrected missense Z score
loeuffloatloss of function observed/expected upper bound fraction (LOEUF)

ClinGen Disease Validity

"clingenGeneValidity":[
{
"diseaseId":"MONDO_0007893",
"disease":"Noonan syndrome with multiple lentigines",
"classification":"no reported evidence",
"classificationDate":"2018-06-07"
},
{
"diseaseId":"MONDO_0015280",
"disease":"cardiofaciocutaneous syndrome",
"classification":"no reported evidence",
"classificationDate":"2018-06-07"
}
]
FieldTypeNotes
clingenGeneValidityobject
diseaseIdstringMonarch Disease Ontology ID (MONDO)
diseasestringdisease label
classificationstringsee below for possible values
classificationDatestringyyyy-MM-dd

classification

  • no reported evidence
  • disputed
  • limited
  • moderate
  • definitive
  • strong
  • refuted