Version: 3.2.5

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.

{ 
   "header":{ 
      "annotator":"Nirvana 3.2.5",
      "creationTime":"2022-12-05 16:43:41",
      "genomeAssembly":"GRCh37",
      "schemaVersion":6,
      "dataVersion":"91.26.50",
      "dataSources":[ 
         { 
            "name":"VEP",
            "version":"91",
            "description":"RefSeq",
            "releaseDate":"2018-03-05"
         },
         { 
            "name":"ClinVar",
            "version":"20190204",
            "description":"A freely accessible, public archive of reports of the relationships among human variations and phenotypes, with supporting evidence",
            "releaseDate":"2019-02-04"
         }
      ],
      "samples":[ 
         "NA12878",
         "NA12891",
         "NA12892"
      ]
   },

Field	Type	Notes
annotator	string	the name of the annotator and the current version
creationTime	string	yyyy-MM-dd hh:mm:ss
genomeAssembly	string	see possible values below
schemaVersion	integer	incremented whenever the core structure of the JSON file introduces breaking changes
dataVersion	string
dataSources	object array	see Data Source entry below
samples	string array	the order of these sample names will be used throughout the JSON file when enumerating samples

Data Source

Field	Type	Notes
name	string
version	string
description	string	optional description of the data source
releaseDate	string	yyyy-MM-dd

Genome Assemblies

GRCh37
GRCh38
hg19

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",

Field	Type	Variant Type	Notes
chromosome	string	all	exactly as displayed in the vcf
postion	integer	all	exactly as displayed in the vcf (1-based notation). Range: 1 - 250 million
repeatUnit	string	STR	provided by ExpansionHunter
refRepeatCount	integer	STR	provided by ExpansionHunter
svEnd	integer	SV
refAllele	string	all	exactly as displayed in the vcf
altAllele	string array	all	exactly as displayed in the vcf
quality	float	all	exactly as displayed in the vcf (Normally an integer, but some variant callers using floating point. Has been observed as high as 500k)
filters	string array	all	exactly as displayed in the vcf
ciPos	integer array	SV
ciEnd	integer array	SV
svLength	integer	SV
strandBias	float	small variant	provided by GATK (from SB)
jointSomaticNormalQuality	integer	SV	provided by the Manta variant caller (SOMATICSCORE)
cytogeneticBand	string	all	e.g. 17p13.1

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
   }
],

Field	Type	Notes
chromosome	string
begin	integer
end	integer
variantType	string
id	string
allAn	floating point	allele number for all populations. Non-zero integer.
allAc	floating point	allele count for all populations. Integer.
allAf	floating point	allele frequency for all populations. Range: 0 - 1.0
afrAf	floating point	allele frequency for the African super population. Range: 0 - 1.0
amrAf	floating point	allele frequency for the Ad Mixed American super population. Range: 0 - 1.0
eurAf	floating point	allele frequency for the European super population. Range: 0 - 1.0
easAf	integer	allele frequency for the East Asian super population. Range: 0 - 1.0
sasAf	integer	allele frequency for the South Asian super population. Range: 0 - 1.0
reciprocalOverlap	floating point	range: 0 - 1.

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
      ],
      "diseaseAffectedStatuses":[
         "-"
      ],
      "artifactAdjustedQualityScore":89.3,
      "likelihoodRatioQualityScore":78.2
   }
]

Field	Type	Notes
genotype	string
repeatNumbers	string	ExpansionHunter-specific
repeatNumberSpans	string	ExpansionHunter-specific
variantFrequencies	float array	range: 0 - 1.0. One value per alternate allele
totalDepth	integer	non-negative integer values
genotypeQuality	integer	non-negative integer values. Typically maxes out at 99
copyNumber	integer	non-negative integer values
alleleDepths	integer array	non-negative integer values
failedFilter	bool
splitReadCounts	integer array	Manta-specific
pairedEndReadCounts	integer array	Manta-specific
lossOfHeterozygosity	bool
deNovoQuality	float
mpileupAlleleDepths	int array	SMN1-specific
silentCarrierHaplotype	string	SMN1-specific
paralogousEntrezGeneIds	int array	SMN1-specific
paralogousGeneCopyNumbers	int array	SMN1-specific
diseaseClassificationSources	string array	SMN1-specific
diseaseIds	string array	SMN1-specific
diseaseAffectedStatuses	string array	SMN1-specific
proteinAlteringVariantPositions	int array	SMN1-specific
isCompoundHetCompatible	bool	SMN1-specific
artifactAdjustedQualityScore	float	PEPE-specific. Range: 0 - 100.0
likelihoodRatioQualityScore	float	PEPE-specific. Range: 0 - 100.0

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,
      "hgvsg":"NC_000002.11:g.48010488G>A",
      "phylopScore":0.459

Field	Type	Notes
vid	string	see Variant Identifiers
chromosome	string
begin	int	1-based non-negative integer values. Range: 1 - 250 million
end	int	1-based non-negative integer values. Range: 1 - 250 million
isReferenceMinorAllele	bool	true when this is a reference minor allele
isStructuralVariant	bool	true when the variant is a structural variant
refAllele	string	parsimonious representation of the reference allele
altAllele	string	parsimonious representation of the alternate allele.
variantType	string	uses Sequence Ontology sequence alterations
isDecomposedVariant	bool	true when the decomposed variant has been used to create another recomposed variant
isRecomposedVariant	bool	true when the variant is recomposed from two or more decomposed variants
hgvsg	string	HGVS g. notation
phylopScore	float	phyloP 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
   }
]

Field	Type	Notes
transcript	string	transcript ID. e.g. ENST00000445503.1
source	string	RefSeq / Ensembl
bioType	string	descriptions of the biotypes from Ensembl
codons	string
aminoAcids	string
cdnaPos	string
cdsPos	string
exons	string	exons affected by the variant
introns	string	introns affected by the variant
proteinPos	string
geneId	string	gene ID. e.g. ENSG00000116062
hgnc	string	gene symbol. e.g. MSH6
consequence	string array	Sequence Ontology Consequences
hgvsc	string	HGVS coding nomenclature
hgvsp	string	HGVS protein nomenclature
geneFusion	object	see Gene Fusions entry below
isCanonical	bool	true when this is a canonical transcript
polyPhenScore	float	range: 0 - 1.0
polyPhenPrediction	string	see possible values below
proteinId	string	protein ID. E.g. ENSP00000405294.1
siftScore	float	range: 0 - 1.0
siftPrediction	string	see possible values below
completeOverlap	bool	true 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

Gene Fusions

Field	Type	Notes
exon	int	actual exon where the breakpoint was located
intron	int	actual intron where the breakpoint was located
fusions	object array	see Fusion entry below

Fusion

Field	Type	Notes
exon	int	actual exon where the other breakpoint was located
intron	int	actual intron where the other breakpoint was located
hgvsc	string	HGVS 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"
      ]
   }
]

Field	Type	Notes
id	string
type	string	see possible values below
consequence	string array	see 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":"RCV000030258.4",
      "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
   }
]

Field	Type	Notes
id	string	ClinVar ID
reviewStatus	string	see possible values below
alleleOrigins	string array	see possible values below
refAllele	string
altAllele	string
phenotypes	string array
medGenIds	string array	MedGen IDs
omimIds	string array	OMIM IDs
orphanetIds	string array	Orphanet IDs
significance	string array	see possible values below
lastUpdatedDate	string	yyyy-MM-dd
pubMedIds	string array	PubMed IDs
isAlleleSpecific	bool	true 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
}

Field	Type	Notes
allAf	float	allele frequency for all populations. Range: 0 - 1.0
allAc	int	allele count for all populations. Integer.
allAn	int	allele number for all populations. Non-zero integer.
afrAf	float	allele frequency for the African super population. Range: 0 - 1.0
afrAc	int	allele count for the African super population. Integer.
afrAn	int	allele number for the African super population. Non-zero integer.
amrAf	float	allele frequency for the Ad Mixed American super population. Range: 0 - 1.0
amrAc	int	allele count for the Ad Mixed American super population. Integer.
amrAn	int	allele number for the Ad Mixed American super population. Non-zero integer.
easAf	float	allele frequency for the East Asian super population. Range: 0 - 1.0
easAc	int	allele count for the East Asian super population. Integer.
easAn	int	allele number for the East Asian super population. Non-zero integer.
eurAf	float	allele frequency for the European super population. Range: 0 - 1.0
eurAc	int	allele count for the European super population. Integer.
eurAn	int	allele number for the European super population. Non-zero integer.
sasAf	float	allele frequency for the South Asian super population. Range: 0 - 1.0
sasAc	int	allele count for the South Asian super population. Integer.
sasAn	int	allele number for the South Asian super population. Non-zero integer.

gnomAD (genomes)

"gnomad":{ 
   "coverage":20,
   "allAf":0.190317,
   "afrAf":0.222876,
   "amrAf":0.121394,
   "easAf":0.239802,
   "finAf":0.136833,
   "nfeAf":0.181282,
   "asjAf":0.258278,
   "othAf":0.186094,
   "allAn":30796,
   "afrAn":8664,
   "amrAn":832,
   "easAn":1618,
   "finAn":3486,
   "nfeAn":14916,
   "asjAn":302,
   "othAn":978,
   "allAc":5861,
   "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,
   "failedFilter":true
}

Field	Type	Notes
coverage	int	average coverage (non-negative integer values)
allAf	float	allele frequency for all populations. Range: 0 - 1.0
allAc	int	allele count for all populations. Integer.
allAn	int	allele number for all populations. Non-zero integer.
allHc	int	count of homozygous individuals for all populations. Non-negative integer.
afrAf	float	allele frequency for the African / African American population. Range: 0 - 1.0
afrAc	int	allele count for the African / African American population. Integer.
afrAn	int	allele number for the African / African American population. Non-zero integer.
afrHc	int	count of homozygous individuals for African / African American population. Non-negative integer.
amrAf	float	allele frequency for the Latino population. Range: 0 - 1.0
amrAc	int	allele count for the Latino population. Integer.
amrAn	int	allele number for the Latino population. Non-zero integer.
amrHc	int	count of homozygous individuals for Latino population. Non-negative integer.
easAf	float	allele frequency for the East Asian population. Range: 0 - 1.0
easAc	int	allele count for the East Asian population. Integer.
easAn	int	allele number for the East Asian population. Non-zero integer.
easHc	int	count of homozygous individuals for East Asian population. Non-negative integer.
finAf	float	allele frequency for the Finnish population. Range: 0 - 1.0
finAc	int	allele count for the Finnish population. Integer.
finAn	int	allele number for the Finnish population. Non-zero integer.
finHc	int	count of homozygous individuals for Finnish population. Non-negative integer
nfeAf	float	allele frequency for the Non-Finnish European population. Range: 0 - 1.0
nfeAc	int	allele count for the Non-Finnish European population. Integer.
nfeAn	int	allele number for the Non-Finnish European population. Non-zero integer.
nfeHc	int	count of homozygous individuals for Non-Finnish European population. Non-negative integer
othAf	float	allele frequency for the Other population. Range: 0 - 1.0
othAc	int	allele count for the Other population. Integer.
othAn	int	allele number for the Other population. Non-zero integer.
othHc	int	count of homozygous individuals for Other population. Non-negative integer
asjAf	float	allele frequency for the Ashkenazi Jewish population. Range: 0 - 1.0
asjAc	int	allele count for the Ashkenazi Jewish population Integer.
asjAn	int	allele number for the Ashkenazi Jewish population. Non-zero integer.
asjHc	int	count of homozygous individuals for the Ashkenazi Jewish population. Non-negative integer
failedFilter	bool	True if this variant failed any filters (Note: we do not list the failed filters)

gnomAD (exomes)

"gnomadExome":{ 
   "coverage":20,
   "allAf":0.190317,
   "afrAf":0.222876,
   "amrAf":0.121394,
   "easAf":0.239802,
   "finAf":0.136833,
   "nfeAf":0.181282,
   "asjAf":0.258278,
   "othAf":0.186094,
   "allAn":30796,
   "afrAn":8664,
   "amrAn":832,
   "easAn":1618,
   "finAn":3486,
   "nfeAn":14916,
   "asjAn":302,
   "othAn":978,
   "allAc":5861,
   "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,
   "failedFilter":true
}

Field	Type	Notes
coverage	int	average coverage (non-negative integer values)
allAf	float	allele frequency for all populations. Range: 0 - 1.0
allAc	int	allele count for all populations. Integer.
allAn	int	allele number for all populations. Non-zero integer.
allHc	int	count of homozygous individuals for all populations. Non-negative integer.
afrAf	float	allele frequency for the African / African American population. Range: 0 - 1.0
afrAc	int	allele count for the African / African American population. Integer.
afrAn	int	allele number for the African / African American population. Non-zero integer.
afrHc	int	count of homozygous individuals for African / African American population. Non-negative integer.
amrAf	float	allele frequency for the Latino population. Range: 0 - 1.0
amrAc	int	allele count for the Latino population. Integer.
amrAn	int	allele number for the Latino population. Non-zero integer.
amrHc	int	count of homozygous individuals for Latino population. Non-negative integer.
easAf	float	allele frequency for the East Asian population. Range: 0 - 1.0
easAc	int	allele count for the East Asian population. Integer.
easAn	int	allele number for the East Asian population. Non-zero integer.
easHc	int	count of homozygous individuals for East Asian population. Non-negative integer.
finAf	float	allele frequency for the Finnish population. Range: 0 - 1.0
finAc	int	allele count for the Finnish population. Integer.
finAn	int	allele number for the Finnish population. Non-zero integer.
finHc	int	count of homozygous individuals for Finnish population. Non-negative integer
nfeAf	float	allele frequency for the Non-Finnish European population. Range: 0 - 1.0
nfeAc	int	allele count for the Non-Finnish European population. Integer.
nfeAn	int	allele number for the Non-Finnish European population. Non-zero integer.
nfeHc	int	count of homozygous individuals for Non-Finnish European population. Non-negative integer
othAf	float	allele frequency for the Other population. Range: 0 - 1.0
othAc	int	allele count for the Other population. Integer.
othAn	int	allele number for the Other population. Non-zero integer.
othHc	int	count of homozygous individuals for Other population. Non-negative integer
asjAf	float	allele frequency for the Ashkenazi Jewish population. Range: 0 - 1.0
asjAc	int	allele count for the Ashkenazi Jewish population Integer.
asjAn	int	allele number for the Ashkenazi Jewish population. Non-zero integer.
asjHc	int	count of homozygous individuals for the Ashkenazi Jewish population. Non-negative integer
sasAf	float	allele frequency for the South Asian population. Range: 0 - 1.0
sasAc	int	allele count for the South Asian population Integer.
sasAn	int	allele number for the South Asian population. Non-zero integer.
sasHc	int	count of homozygous individuals for the South Asian population. Non-negative integer.
failedFilter	bool	True if this variant failed any filters (Note: we do not list the failed filters)

dbSNP

"dbsnp":[
   "rs1042821"
]

Field	Type	Notes
dbsnp	string array	dbSNP rsIDs

Overview​

Conventions​

JSON Layout​

info

Header​

Data Source​

Genome Assemblies​

Positions​

1000 Genomes (SV)​

Samples​

Empty Samples

Variants​

Reference Minor Alleles

Flagging Decomposed & Recomposed Variants

Transcripts​

PolyPhen​

SIFT​

Gene Fusions​

Fusion​

Regulatory Regions​

Regulatory Types​

Regulatory Consequences​

ClinVar​

1000 Genomes​

gnomAD (genomes)​

gnomAD (exomes)​

dbSNP​

Overview

Conventions

JSON Layout

Header

Data Source

Genome Assemblies

Positions

1000 Genomes (SV)

Samples

Variants

Transcripts

PolyPhen

SIFT

Gene Fusions

Fusion

Regulatory Regions

Regulatory Types

Regulatory Consequences

ClinVar

1000 Genomes

gnomAD (genomes)

gnomAD (exomes)

dbSNP