[ensembl-dev] VEP SV annotation

Wed Aug 25 16:30:04 BST 2021

Hi,

I am using VEP to annotate nssv15852771, and I notice that VEP annotates the transcript IMPACT as MODIFIER, but gnomad reports this sv variant as loss of function, https://gnomad.broadinstitute.org/variant/DEL_1_3860?dataset=gnomad_sv_r2_1,
since it knocks out exon 1 which is also coding.

Here is the vcf output from VEP:

##fileformat=VCFv4.1
##VEP="v104" time="2021-08-25 14:58:12" cache="/net/isilonP/public/ro/ensweb-data/latest/tools/www/e104/vep/cache/homo_sapiens_refseq/104_GRCh38" db="homo_sapiens_core_104_38 at hh-mysql-ens-species-web-1" 1000genomes="phase3" COSMIC="92" ClinVar="20210102" ESP="V2-SSA137" HGMD-PUBLIC="20204" assembly="GRCh38.p13" dbSNP="154" gencode="GENCODE 38" genebuild="2014-07" gnomAD="r2.1.1" polyphen="2.2.2" refseq="2020-12-10 18:46:50 - GCF_000001405.39_GRCh38.p13_genomic.gff" regbuild="1.0" sift="sift5.2.2"
##INFO=<ID=CSQ,Number=.,Type=String,Description="Consequence annotations from Ensembl VEP. Format: Allele|Consequence|IMPACT|SYMBOL|Gene|Feature_type|Feature|BIOTYPE|EXON|INTRON|HGVSc|HGVSp|cDNA_position|CDS_position|Protein_position|Amino_acids|Codons|Existing_variation|DISTANCE|STRAND|FLAGS|SYMBOL_SOURCE|HGNC_ID|MANE_SELECT|MANE_PLUS_CLINICAL|TSL|APPRIS|REFSEQ_MATCH|REFSEQ_OFFSET|GIVEN_REF|USED_REF|BAM_EDIT|AF|CLIN_SIG|SOMATIC|PHENO|PUBMED">
#CHROM             POS        ID           REF        ALT        QUAL    FILTER   INFO
chr1       55029217             nssv15852771    G            <DEL>   .               .              SVTYPE=DEL;END=55043368;SVLEN=-14152;CSQ=deletion|coding_sequence_variant&5_prime_UTR_variant&intron_variant&feature_truncation|MODIFIER|PCSK9|255738|Transcript|NM_174936.4|protein_coding|1/12|1/11||||||||||1||EntrezGene||ENST00000302118.5|||||||||||||,deletion|non_coding_transcript_exon_variant&intron_variant&feature_truncation|MODIFIER|PCSK9|255738|Transcript|NR_110451.2|misc_RNA|1/10|1/9||||||||||1||EntrezGene|||||||||||||||

Is there any valid reason why VEP does not annotate this as HIGH IMPACT,or is this a bug in VEP ?

Best regards,

Sigurjon A. Gudjonsson
Bioinformatics Group
Decode Genetics
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