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.
Impact | Definition |
---|---|
high | The variant is assumed to have high (disruptive) impact in the protein, probably causing protein truncation, loss of function or triggering nonsense mediated decay. |
moderate | A non-disruptive variant that might change protein effectiveness. |
low | Assumed to be mostly harmless or unlikely to change protein behavior. |
modifier | Usually 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.
- SnpEff Documentation and Codebase
- VEP Documentation
Consequence Impacts
Following table gives the combined rating for all consequences recognized by Illumina Connected Annotations.
Consequence | SnpEff Impact | VEP Impact | Illumina Connected Annotations Impact | Comment |
---|---|---|---|---|
bidirectional_gene_fusion | high | high | SnpEff | |
coding_sequence_variant | low, modifier | modifier | modifier | Based on CDS |
copy_number_change | modifier | |||
copy_number_decrease | modifier | |||
copy_number_increase | modifier | |||
downstream_gene_variant | modifier | modifier | modifier | SnpEff + VEP |
feature_elongation | modifier | high | high | VEP |
feature_truncation | high | high | VEP | |
five_prime_duplicated_transcript | modifier | |||
five_prime_UTR_variant | modifier | modifier | modifier | SnpEff + VEP |
frameshift_variant | high | high | high | SnpEff + VEP |
gene_fusion | high | high | SnpEff | |
incomplete_terminal_codon_variant | low | low | VEP | |
inframe_deletion | moderate | moderate | moderate | SnpEff + VEP |
inframe_insertion | moderate | moderate | moderate | SnpEff + VEP |
intron_variant | modifier | modifier | modifier | SnpEff + VEP |
mature_miRNA_variant | modifier | modifier | VEP | |
missense_variant | moderate | moderate | moderate | SnpEff + VEP |
NMD_transcript_variant | modifier | modifier | VEP | |
non_coding_transcript_exon_variant | modifier | modifier | modifier | SnpEff + VEP |
non_coding_transcript_variant | modifier | modifier | modifier | SnpEff + VEP |
protein_altering_variant | moderate | moderate | VEP | |
regulatory_region_ablation | modifier | modifier | VEP | |
regulatory_region_amplification | modifier | modifier | VEP | |
regulatory_region_variant | modifier | modifier | modifier | SnpEff + VEP |
short_tandem_repeat_change | modifier | |||
short_tandem_repeat_contraction | modifier | |||
short_tandem_repeat_expansion | modifier | |||
splice_acceptor_variant | high | high | high | SnpEff + VEP |
splice_donor_variant | high | high | high | SnpEff + VEP |
splice_region_variant | moderate, low | low | low | Based on SPLICE_SITE_REGION in SnpEff |
start_lost | high | high | high | SnpEff + VEP |
start_retained_variant | low | low | low | SnpEff + VEP |
stop_gained | high | high | high | SnpEff + VEP |
stop_lost | high | high | high | SnpEff + VEP |
stop_retained_variant | low | low | low | SnpEff + VEP |
synonymous_variant | low | low | low | SnpEff + VEP |
three_prime_duplicated_transcript | modifier | |||
three_prime_UTR_variant | modifier | modifier | modifier | SnpEff + VEP |
transcript_ablation | high | high | high | SnpEff + VEP |
transcript_amplification | high | high | VEP | |
transcript_variant | modifier | modifier | SnpEff | |
unidirectional_gene_fusion | high | high | SnpEff | |
upstream_gene_variant | modifier | modifier | modifier | SnpEff + VEP |
Note:
- For transcripts with multiple consequences, the most severe impact rating is chosen.
- 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"
}
]
}
]
}