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Version: 3.22

Transcript Consequence Impact

Overview

Illumina Connected Annotations provides transcript consequence impacts from SnpEff.

Following definitions are used for the impact ratings as obtained from SnpEff.

ImpactDefinition
highThe variant is assumed to have high (disruptive) impact in the protein, probably causing protein truncation, loss of function or triggering nonsense mediated decay.
moderateA non-disruptive variant that might change protein effectiveness.
lowAssumed to be mostly harmless or unlikely to change protein behavior.
modifierUsually non-coding variants or variants affecting non-coding genes, where predictions are difficult or there is no evidence of impact.

Sources

Not all consequences are rated by SnpEff, therefore Illumina Connected Annotations combines the ratings from SnpEff with those from VEP.

  1. SnpEff Documentation and Codebase
  2. VEP Documentation

Consequence Impacts

Following table gives the combined rating for all consequences recognized by Illumina Connected Annotations.

ConsequenceSnpEff ImpactVEP ImpactIllumina Connected Annotations ImpactComment
bidirectional_gene_fusionhighhighSnpEff
coding_sequence_variantlow, modifiermodifiermodifierBased on CDS
copy_number_changemodifier
copy_number_decreasemodifier
copy_number_increasemodifier
downstream_gene_variantmodifiermodifiermodifierSnpEff + VEP
feature_elongationmodifierhighhighVEP
feature_truncationhighhighVEP
five_prime_duplicated_transcriptmodifier
five_prime_UTR_variantmodifiermodifiermodifierSnpEff + VEP
frameshift_varianthighhighhighSnpEff + VEP
gene_fusionhighhighSnpEff
incomplete_terminal_codon_variantlowlowVEP
inframe_deletionmoderatemoderatemoderateSnpEff + VEP
inframe_insertionmoderatemoderatemoderateSnpEff + VEP
intron_variantmodifiermodifiermodifierSnpEff + VEP
mature_miRNA_variantmodifiermodifierVEP
missense_variantmoderatemoderatemoderateSnpEff + VEP
NMD_transcript_variantmodifiermodifierVEP
non_coding_transcript_exon_variantmodifiermodifiermodifierSnpEff + VEP
non_coding_transcript_variantmodifiermodifiermodifierSnpEff + VEP
protein_altering_variantmoderatemoderateVEP
regulatory_region_ablationmodifiermodifierVEP
regulatory_region_amplificationmodifiermodifierVEP
regulatory_region_variantmodifiermodifiermodifierSnpEff + VEP
short_tandem_repeat_changemodifier
short_tandem_repeat_contractionmodifier
short_tandem_repeat_expansionmodifier
splice_acceptor_varianthighhighhighSnpEff + VEP
splice_donor_varianthighhighhighSnpEff + VEP
splice_region_variantmoderate, lowlowlowBased on SPLICE_SITE_REGION in SnpEff
start_losthighhighhighSnpEff + VEP
start_retained_variantlowlowlowSnpEff + VEP
stop_gainedhighhighhighSnpEff + VEP
stop_losthighhighhighSnpEff + VEP
stop_retained_variantlowlowlowSnpEff + VEP
synonymous_variantlowlowlowSnpEff + VEP
three_prime_duplicated_transcriptmodifier
three_prime_UTR_variantmodifiermodifiermodifierSnpEff + VEP
transcript_ablationhighhighhighSnpEff + VEP
transcript_amplificationhighhighVEP
transcript_variantmodifiermodifierSnpEff
unidirectional_gene_fusionhighhighSnpEff
upstream_gene_variantmodifiermodifiermodifierSnpEff + VEP
Note:
  1. For transcripts with multiple consequences, the most severe impact rating is chosen.
  2. In case of consequences that do not have any impact rating from SnpEff or VEP, Illumina Connected Annotations provides modifier.

Known Issues

Known Issues

The consequence splice_polypyrimidine_tract_variant, is rated as low by VEP. However, this consequence is not annotated by Illumina Connected Annotations, therefore the impact will also not be provided.

Example Transcript

The key impact for each transcript gives the impact rating for the consequence.

{
"variants": [
{
"vid": "1-1623412-T-C",
"chromosome": "1",
"begin": 1623412,
"end": 1623412,
"refAllele": "T",
"altAllele": "C",
"variantType": "SNV",
"hgvsg": "NC_000001.11:g.1623412T>C",
"transcripts": [
{
"transcript": "ENST00000479659.5",
"source": "Ensembl",
"bioType": "lncRNA",
"introns": "2/18",
"geneId": "ENSG00000197530",
"hgnc": "MIB2",
"consequence": [
"intron_variant",
"non_coding_transcript_variant"
],
"impact": "modifier",
"hgvsc": "ENST00000479659.5:n.288-19T>C"
},
{
"transcript": "ENST00000489635.5",
"source": "VEP",
"bioType": "mRNA",
"codons": "aTg/aCg",
"aminoAcids": "M/T",
"cdnaPos": "269",
"cdsPos": "134",
"exons": "3/20",
"proteinPos": "45",
"geneId": "ENSG00000197530",
"hgnc": "MIB2",
"consequence": [
"missense_variant"
],
"impact": "moderate",
"hgvsc": "ENST00000489635.5:c.134T>C",
"hgvsp": "ENSP00000426007.1:p.(Met45Thr)",
"proteinId": "ENSP00000426007.1"
}
]
}
]
}