[ensembl-dev] CNV IMPACT

Thu Oct 28 13:38:49 BST 2021

Hi Amandine,

The IMPACT column is a subjective classification of the severity of the 
variant consequence. It is a separate rating given for compatibility 
with other variant annotation tools e.g. snpEff. As this rating is 
subjective, you can always get the full set of consequences for each 
allele and make your own severity judgement.

Information on all of our consequences can be found here: 
https://www.ensembl.org/info/genome/variation/prediction/predicted_data.html 
<https://www.ensembl.org/info/genome/variation/prediction/predicted_data.html>

Best wishes,

Diana

On 28/10/2021 08:44, AMANDINE SEPTIER wrote:
> Hello VEP team,
>
> Thank you very much for your tool.
> I send you this mail because I'm analyzing Exome data and making CNV 
> calls on a patients cohort.
> When I annotate SVs with VEP, it returns "MODIFIER" hits for CNVs 
> covering several exons/introns without covering the entire impacted 
> gene(s).(details below)
> Some of them are experimentally validated, so it is a pity that VEP 
> doesn't send back these CNVs. (ex : CFAP251)
> Is it possible to put more weight on the 'feature_truncation' or 
> 'feature_elongation' variants consequences so that they have a greater 
> impact?
> This is just a discussion I'm opening up.
> Thanks in advance for your future return.
> Regards.
> -- 
> ----------------------------------------------------------------------
> Amandine SEPTIER
> Doctorante
> Laboratoire TIMC-IMAG/MAGe, CNRS UMR 5525
> Pavillon Taillefer, Faculté de Médecine
> 38700 La Tronche, France
> ---------------------------------------------------------------
>
> VCF INPUT:
> ##fileformat=VCFv4.3
> ##fileDate=20211027
> ##ALT=<ID=DEL,Description="Deletion">
> ##ALT=<ID=DUP,Description="Duplication">
> ##ALT=<ID=CNV,Description="Copy number variable region">
> ##INFO=<ID=SVTYPE,Number=1,Type=String,Description="Type of structural 
> variant">
> ##INFO=<ID=END,Number=1,Type=Integer,Description="End position of the 
> variant described in this record">
> ##FORMAT=<ID=GT,Number=1,Type=Integer,Description="Genotype">
> ##FORMAT=<ID=CN,Number=1,Type=Integer,Description="Copy number 
> genotype for imprecise events">
> #CHROM    POS    ID    REF    ALT    QUAL FILTER    INFO    FORMAT    
> S1    S2    S3
> 4    146867498 <callto:4 146867498> TTC29_HetDEL    .    <DEL>    .    
> . SVTYPE=DEL;END=146867583    GT:CN    0/1:1 ./.:2    ./.:2
> 12    121908103 <callto:12 121908103> CFAP251_AllGene    .    <DEL>    
> .    . SVTYPE=DEL;END=122003919    GT:CN    1/1:0 1/1:0    1/1:0
> 12    121999716 <callto:12 121999716> CFAP251_HomoDEL    .    <DEL>    
> .    . SVTYPE=DEL;END=122001598    GT:CN    1/1:0 1/1:0    1/1:0
> 12    121999716 <callto:12 121999716> CFAP251_exon20/22    .    
> <DEL>    .    . SVTYPE=DEL;END=121999944    GT:CN    1/1:0 1/1:0    1/1:0
> 12    122001497 <callto:12 122001497> CFAP251_exon21/22    .    
> <DEL>    .    . SVTYPE=DEL;END=122001598    GT:CN    1/1:0 1/1:0    1/1:0
>
> COMMAND LINE:
> vep -i VEPtest_211027.vcf --cache --offline --force_overwrite --format 
> vcf --vcf -o OutVEP_211027.csv
>
> OUTPUT
> ##fileformat=VCFv4.3
> ##fileDate=20211027
> ##ALT=<ID=DEL,Description="Deletion">
> ##ALT=<ID=DUP,Description="Duplication">
> ##ALT=<ID=CNV,Description="Copy number variable region">
> ##INFO=<ID=SVTYPE,Number=1,Type=String,Description="Type of structural 
> variant">
> ##INFO=<ID=END,Number=1,Type=Integer,Description="End position of the 
> variant described in this record">
> ##FORMAT=<ID=GT,Number=1,Type=Integer,Description="Genotype">
> ##FORMAT=<ID=CN,Number=1,Type=Integer,Description="Copy number 
> genotype for imprecise events">
> ##VEP="v104" time="2021-10-27 11 <callto:2021-10-27 11>:56:04" 
> cache="/home/septiera/.vep/homo_sapiens/104_GRCh38" 
> ensembl-funcgen=104.59ae779 ensembl-variation=104.6154f8b 
> ensembl=104.1af1dce ensembl-io=104.1d3bb6e 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" 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">
> #CHROM    POS    ID    REF    ALT    QUAL FILTER    INFO    FORMAT    
> S1    S2    S3
> 4    146867498 <callto:4 146867498> TTC29_HetDEL    .    <DEL>    .    
> . 
> SVTYPE=DEL;END=146867583;CSQ=deletion|frameshift_variant&feature_truncation|HIGH|TTC29|ENSG00000137473|Transcript|ENST00000325106|protein_coding|8/13||||1009-1093|800-884|267-295|||||-1||HGNC|HGNC:29936,deletion|frameshift_variant&feature_truncation|HIGH|TTC29|ENSG00000137473|Transcript|ENST00000504425|protein_coding|8/13||||1027-1111|800-884|267-295|||||-1||HGNC|HGNC:29936,deletion|frameshift_variant&NMD_transcript_variant&feature_truncation|HIGH|TTC29|ENSG00000137473|Transcript|ENST00000508306|nonsense_mediated_decay|8/14||||978-1062|800-884|267-295|||||-1||HGNC|HGNC:29936,deletion|frameshift_variant&feature_truncation|HIGH|TTC29|ENSG00000137473|Transcript|ENST00000513335|protein_coding|9/14||||1078-1162|878-962|293-321|||||-1||HGNC|HGNC:29936 
> GT:CN    0/1:1    ./.:2    ./.:2
> 12    121908103 <callto:12 121908103> CFAP251_AllGene    .    <DEL>    
> .    . 
> SVTYPE=DEL;END=122003919;CSQ=deletion|stop_lost&coding_sequence_variant&3_prime_UTR_variant&intron_variant&feature_truncation|HIGH|PSMD9|ENSG00000110801|Transcript|ENST00000261817|protein_coding|5-6/6|4-5/5||||||||||1||HGNC|HGNC:9567,deletion|transcript_ablation|HIGH|CFAP251|ENSG00000158023|Transcript|ENST00000288912|protein_coding||||||||||||1||HGNC|HGNC:28506,deletion|transcript_ablation|HIGH|PSMD9|ENSG00000110801|Transcript|ENST00000361485|retained_intron||||||||||||1||HGNC|HGNC:9567,deletion|transcript_ablation|HIGH|CFAP251|ENSG00000158023|Transcript|ENST00000397454|protein_coding||||||||||||1||HGNC|HGNC:28506,deletion|transcript_ablation|HIGH|CFAP251|ENSG00000158023|Transcript|ENST00000428465|retained_intron||||||||||||1||HGNC|HGNC:28506,deletion|non_coding_transcript_exon_variant&feature_truncation|MODIFIER|RNU7-170P|ENSG00000239082|Transcript|ENST00000459303|snRNA|1/1||||2-?|||||||1||HGNC|HGNC:45704,deletion|transcript_ablation|HIGH|CFAP251|ENSG00000158023|Transcript|ENST00000535257|retained_intron||||||||||||1||HGNC|HGNC:28506,deletion|3_prime_UTR_variant&intron_variant&NMD_transcript_variant&feature_truncation|MODIFIER|PSMD9|ENSG00000110801|Transcript|ENST00000535293|nonsense_mediated_decay|4-5/5|3-4/4||||||||||1||HGNC|HGNC:9567,deletion|stop_lost&coding_sequence_variant&3_prime_UTR_variant&intron_variant&NMD_transcript_variant&feature_truncation|HIGH|PSMD9|ENSG00000110801|Transcript|ENST00000537407|nonsense_mediated_decay|5-7/7|4-6/6||||||||||1||HGNC|HGNC:9567,deletion|downstream_gene_variant|MODIFIER||ENSG00000255856|Transcript|ENST00000538710|lncRNA|||||||||||3515|-1|||,deletion|transcript_ablation|HIGH|CFAP251|ENSG00000158023|Transcript|ENST00000540779|retained_intron||||||||||||1||HGNC|HGNC:28506,deletion|3_prime_UTR_variant&intron_variant&NMD_transcript_variant&feature_truncation|MODIFIER|PSMD9|ENSG00000110801|Transcript|ENST00000540962|nonsense_mediated_decay|4-5/5|3-4/4||||||||||1||HGNC|HGNC:9567,deletion|stop_lost&coding_sequence_variant&3_prime_UTR_variant&intron_variant&feature_truncation|HIGH|PSMD9|ENSG00000110801|Transcript|ENST00000541212|protein_coding|5-6/6|4-5/5||||||||||1||HGNC|HGNC:9567,deletion|stop_lost&coding_sequence_variant&3_prime_UTR_variant&intron_variant&feature_truncation|HIGH|PSMD9|ENSG00000110801|Transcript|ENST00000542602|protein_coding|3-4/4|2-3/3||||||||||1||HGNC|HGNC:9567,deletion|transcript_ablation|HIGH|CFAP251|ENSG00000158023|Transcript|ENST00000543211|retained_intron||||||||||||1||HGNC|HGNC:28506,deletion|3_prime_UTR_variant&intron_variant&NMD_transcript_variant&feature_truncation|MODIFIER|PSMD9|ENSG00000110801|Transcript|ENST00000543699|nonsense_mediated_decay|5-6/6|4-5/5||||||||||1||HGNC|HGNC:9567,deletion|non_coding_transcript_exon_variant&intron_variant&feature_truncation|MODIFIER|PSMD9|ENSG00000110801|Transcript|ENST00000544254|retained_intron|2-3/3|1-2/2||||||||||1||HGNC|HGNC:9567,deletion|non_coding_transcript_exon_variant&intron_variant&feature_truncation|MODIFIER|PSMD9|ENSG00000110801|Transcript|ENST00000544724|retained_intron|3-4/4|2-3/3||||||||||1||HGNC|HGNC:9567,deletion|transcript_ablation|HIGH||ENSG00000256950|Transcript|ENST00000544911|retained_intron||||||||||||1|||,deletion|transcript_ablation|HIGH|CFAP251|ENSG00000158023|Transcript|ENST00000545752|processed_transcript||||||||||||1||HGNC|HGNC:28506,deletion|non_coding_transcript_exon_variant&intron_variant&feature_truncation|MODIFIER|CFAP251|ENSG00000158023|Transcript|ENST00000545988|processed_transcript|1-2/2|1/1|||?-484|||||||1||HGNC|HGNC:28506,deletion|transcript_ablation|HIGH|CFAP251|ENSG00000158023|Transcript|ENST00000546044|retained_intron||||||||||||1||HGNC|HGNC:28506,deletion|3_prime_UTR_variant&intron_variant&NMD_transcript_variant&feature_truncation|MODIFIER||ENSG00000256950|Transcript|ENST00000546333|nonsense_mediated_decay|4/4|3/3||||||||||1||| 
> GT:CN    1/1:0    1/1:0    1/1:0
> 12    121999716 <callto:12 121999716> CFAP251_HomoDEL    .    <DEL>    
> .    . 
> SVTYPE=DEL;END=122001598;CSQ=deletion|coding_sequence_variant&intron_variant&feature_truncation|MODIFIER|CFAP251|ENSG00000158023|Transcript|ENST00000288912|protein_coding|20-21/22|20/21|||3132-3461|3008-3337|1003-1113|||||1||HGNC|HGNC:28506,deletion|non_coding_transcript_exon_variant&intron_variant&feature_truncation|MODIFIER|CFAP251|ENSG00000158023|Transcript|ENST00000428465|retained_intron|1-2/3|1/2|||2832-3161|||||||1||HGNC|HGNC:28506,deletion|upstream_gene_variant|MODIFIER|CFAP251|ENSG00000158023|Transcript|ENST00000545988|processed_transcript|||||||||||106|1||HGNC|HGNC:28506 
> GT:CN    1/1:0    1/1:0    1/1:0
> 12    121999716 <callto:12 121999716> CFAP251_Corrpad_exon20/22    
> .    <DEL> .    . 
> SVTYPE=DEL;END=121999944;CSQ=deletion|inframe_deletion&feature_truncation|MODERATE|CFAP251|ENSG00000158023|Transcript|ENST00000288912|protein_coding|20/22||||3132-3359|3008-3235|1003-1079|||||1||HGNC|HGNC:28506,deletion|non_coding_transcript_exon_variant&feature_truncation|MODIFIER|CFAP251|ENSG00000158023|Transcript|ENST00000428465|retained_intron|1/3||||2832-3059|||||||1||HGNC|HGNC:28506,deletion|upstream_gene_variant|MODIFIER|CFAP251|ENSG00000158023|Transcript|ENST00000545988|processed_transcript|||||||||||1760|1||HGNC|HGNC:28506 
> GT:CN    1/1:0    1/1:0    1/1:0
> 12    122001497 <callto:12 122001497> CFAP251_Corrpad_exon21/22    
> .    <DEL> .    . 
> SVTYPE=DEL;END=122001598;CSQ=deletion|frameshift_variant&feature_truncation|HIGH|CFAP251|ENSG00000158023|Transcript|ENST00000288912|protein_coding|21/22||||3361-3461|3237-3337|1079-1113|||||1||HGNC|HGNC:28506,deletion|non_coding_transcript_exon_variant&feature_truncation|MODIFIER|CFAP251|ENSG00000158023|Transcript|ENST00000428465|retained_intron|2/3||||3061-3161|||||||1||HGNC|HGNC:28506,deletion|upstream_gene_variant|MODIFIER|CFAP251|ENSG00000158023|Transcript|ENST00000545988|processed_transcript|||||||||||106|1||HGNC|HGNC:28506 
> GT:CN    1/1:0    1/1:0    1/1:0
>
>
>       System
>
>   * VEP version: 104.3
>   * VEP Cache version: homo_sapiens_vep_104_GRCh38
>   * Perl version: perl-5.16.3-299.el7_9.x86_64
>   * OS: centos 7
>   * tabix installed ? yes
>
>
>
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