<p>You need to set your expectations clearly instead of just saying &quot;Does not agree&quot;. I'm taking a guess here - your statement is that the 2/4 of the gene co-ordinates do not overlap the variant location.</p>
<p>This is because you're viewing just part of the picture - the co-ordinates - and not seeing another important part, which is the kind of effect. For the latter two genes, VEP clearly says the effect is <code>downstream_gene_variant</code>, which <a href="http://www.sequenceontology.org/browser/current_svn/term/SO:0001632" rel="nofollow noreferrer">Sequence Ontology defines</a> as &quot;A sequence variant located 3' of a gene.&quot;</p>
<p>Putting those two pieces together, the entire picture makes sense. Variants affect different transcripts (of possibly different genes) in different manners. Looking at just 1 of those 2 components will of course make things seem odd.</p>

CC BY-SA 4.0
2023-11-27T10:22:35.990Z
You are right, it is just overlapping genes. And VEP annotates these, while other variant annotation tools like ANNOVAR do not (just outputs the most deleterious) [ref](https://www.goldenhelix.com/blog/the-sate-of-variant-annotation-a-comparison-of-annovar-snpeff-and-vep/).
Dandelion
CC BY-SA 4.0
2023-11-28T17:35:22.070Z
That’s not true. Both tools can annotate all or most deleterious effects depending on the parameters you use.
Ram RS
CC BY-SA 4.0
2023-11-28T17:42:06.750Z
Just saw the reference post you’d added - that post is wrong. See ANNOVAR documentation- it says “ If the users want to have all functional consequences printed out (rather than just the most important one defined by the precedence above), the --separate argument should be used. In this case, several output lines may be present for each variant, representing several possible functional consequences.”
Ram RS
CC BY-SA 4.0
2023-11-29T11:59:48.917Z
I guess the difference would be the default behavior maybe, but you are right. Sorry for the confusion and thank you for your patience.
Dandelion
CC BY-SA 4.0
2023-11-06T18:21:02.950Z
2023-11-06T18:21:02.950Z
Ram RS
<p>I have a vcf file that I annoteted with VEP, for human data. I have run VEP to annotate my files with some additional parameters (as shown below in the ##VEP-command-line).</p>
<p>However, my output is rather strange (mainly the INFO column).</p>
<pre><code>##VEP=&quot;v108&quot; time=&quot;2023-04-27 15:13:08&quot; cache=&quot;workflow/resources/variants/cache_vep/homo_sapiens/108_GRCh38&quot; ensembl-funcgen=108.56bb136 ensembl-variation=108.a885ada ensembl-io=108.58d13c1 ensembl=108.d8a9c80 1000genomes=&quot;phase3&quot; COSMIC=&quot;96&quot; ClinVar=&quot;202205&quot; HGMD-PUBLIC=&quot;20204&quot; assembly=&quot;GRCh38.p13&quot; dbSNP=&quot;154&quot; gencode=&quot;GENCODE 42&quot; genebuild=&quot;2014-07&quot; gnomADe=&quot;r2.1.1&quot; gnomADg=&quot;v3.1.2&quot; polyphen=&quot;2.2.2&quot; regbuild=&quot;1.0&quot; sift=&quot;sift5.2.2&quot;
##INFO=&lt;ID=CSQ,Number=.,Type=String,Description=&quot;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|GENE_PHENO|SIFT|PolyPhen|AF|AFR_AF|AMR_AF|EAS_AF|EUR_AF|SAS_AF|gnomADe_AF|gnomADe_AFR_AF|gnomADe_AMR_AF|gnomADe_ASJ_AF|gnomADe_EAS_AF|gnomADe_FIN_AF|gnomADe_NFE_AF|gnomADe_OTH_AF|gnomADe_SAS_AF|CLIN_SIG|SOMATIC|PHENO&quot;&gt;
##VEP-command-line='vep --dir_cache workflow/resources/variants/cache_vep --vcf -i WESP_run/results/variant_calling/VP_DBS_25_7_S7.vcf -o WESP_run/results/variant_annotation/VP_DBS_25_7_S7.annotated.vcf.gz --af --af_1kg --af_gnomade --sift b --polyphen b --gene_phenotype --fork 24 --offline --compress_output gzip'
#CHROM  POS ID  REF ALT QUAL    FILTER  INFO    FORMAT  VP_DBS_25_7_S7
chr1    13273   .   G   C   25.3    PASS    CSQ=C|non_coding_transcript_exon_variant|MODIFIER|DDX11L1|ENSG00000223972|Transcript|ENST00000450305|transcribed_unprocessed_pseudogene|5/6||||313|||||rs531730856||1||HGNC|HGNC:37102||||0.0950|0.0204|0.1455|0.0625|0.1471|0.1401||||||||||||,C|non_coding_transcript_exon_variant|MODIFIER|DDX11L2|ENSG00000290825|Transcript|ENST00000456328|lncRNA|3/3||||521|||||rs531730856||1||EntrezGene|||||0.0950|0.0204|0.1455|0.0625|0.1471|0.1401||||||||||||,C|downstream_gene_variant|MODIFIER|WASH7P|ENSG00000227232|Transcript|ENST00000488147|unprocessed_pseudogene||||||||||rs531730856|1131|-1||HGNC|HGNC:38034||||0.0950|0.0204|0.1455|0.0625|0.1471|0.1401||||||||||||,C|downstream_gene_variant|MODIFIER|MIR6859-1|ENSG00000278267|Transcript|ENST00000619216|miRNA||||||||||rs531730856|4096|-1||HGNC|HGNC:50039||||0.0950|0.0204|0.1455|0.0625|0.1471|0.1401|||||||||||| GT:GQ:DP:AD:VAF:PL  0/1:23:55:28,27:0.490909:25,0,27
</code></pre>
<p>For instance, at the first location/variant I look at the Ensembl gene id and see multiple genes on the same locations and strand. This is very strange to me, as I would understand different transcripts, but different genes on the same strand? Also, apart from that, the corresponding locations/regions of genes on the Ensembl website do not agree with the location in the vcf file.
For instance, the location for this SNP is 13273, but the annotations are (corresponding ensembl archive version 108):</p>
<ul>
<li>Agrees: <a href="http://oct2022.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000223972;r=1:12010-13670;t=ENST00000450305" rel="nofollow noreferrer">http://oct2022.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000223972;r=1:12010-13670;t=ENST00000450305</a></li>
<li>Agrees: <a href="http://oct2022.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000290825;r=1:11869-14409;t=ENST00000456328" rel="nofollow noreferrer">http://oct2022.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000290825;r=1:11869-14409;t=ENST00000456328</a></li>
<li>Does not agree: <a href="http://oct2022.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000227232;r=1:14404-29570;t=ENST00000488147" rel="nofollow noreferrer">http://oct2022.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000227232;r=1:14404-29570;t=ENST00000488147</a></li>
<li>Does not agree: <a href="http://oct2022.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000278267;r=1:17369-17436;t=ENST00000619216" rel="nofollow noreferrer">http://oct2022.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000278267;r=1:17369-17436;t=ENST00000619216</a></li>
</ul>
<p>What am I missing here?</p>
<p>Kind regards,
Eva</p>

<vcf><ensembl><identifiers><vep>
VEP annotation INFO field Ensembl IDs and locations
# VEP annotation INFO field Ensembl IDs and locations

(Asked by: username_0 on 2023-11-06)

I have a vcf file that I annoteted with VEP, for human data. I have run VEP to annotate my files with some additional parameters (as shown below in the ##VEP-command-line).
However, my output is rather strange (mainly the INFO column).
##VEP="v108" time="2023-04-27 15:13:08" cache="workflow/resources/variants/cache_vep/homo_sapiens/108_GRCh38" ensembl-funcgen=108.56bb136 ensembl-variation=108.a885ada ensembl-io=108.58d13c1 ensembl=108.d8a9c80 1000genomes="phase3" COSMIC="96" ClinVar="202205" HGMD-PUBLIC="20204" assembly="GRCh38.p13" dbSNP="154" gencode="GENCODE 42" genebuild="2014-07" gnomADe="r2.1.1" gnomADg="v3.1.2" polyphen="2.2.2" regbuild="1.0" sift="sift5.2.2"
##INFO=
##VEP-command-line='vep --dir_cache workflow/resources/variants/cache_vep --vcf -i WESP_run/results/variant_calling/VP_DBS_25_7_S7.vcf -o WESP_run/results/variant_annotation/VP_DBS_25_7_S7.annotated.vcf.gz --af --af_1kg --af_gnomade --sift b --polyphen b --gene_phenotype --fork 24 --offline --compress_output gzip'
#CHROM  POS ID  REF ALT QUAL    FILTER  INFO    FORMAT  VP_DBS_25_7_S7
chr1    13273   .   G   C   25.3    PASS    CSQ=C|non_coding_transcript_exon_variant|MODIFIER|DDX11L1|ENSG00000223972|Transcript|ENST00000450305|transcribed_unprocessed_pseudogene|5/6||||313|||||rs531730856||1||HGNC|HGNC:37102||||0.0950|0.0204|0.1455|0.0625|0.1471|0.1401||||||||||||,C|non_coding_transcript_exon_variant|MODIFIER|DDX11L2|ENSG00000290825|Transcript|ENST00000456328|lncRNA|3/3||||521|||||rs531730856||1||EntrezGene|||||0.0950|0.0204|0.1455|0.0625|0.1471|0.1401||||||||||||,C|downstream_gene_variant|MODIFIER|WASH7P|ENSG00000227232|Transcript|ENST00000488147|unprocessed_pseudogene||||||||||rs531730856|1131|-1||HGNC|HGNC:38034||||0.0950|0.0204|0.1455|0.0625|0.1471|0.1401||||||||||||,C|downstream_gene_variant|MODIFIER|MIR6859-1|ENSG00000278267|Transcript|ENST00000619216|miRNA||||||||||rs531730856|4096|-1||HGNC|HGNC:50039||||0.0950|0.0204|0.1455|0.0625|0.1471|0.1401|||||||||||| GT:GQ:DP:AD:VAF:PL  0/1:23:55:28,27:0.490909:25,0,27

For instance, at the first location/variant I look at the Ensembl gene id and see multiple genes on the same locations and strand. This is very strange to me, as I would understand different transcripts, but different genes on the same strand? Also, apart from that, the corresponding locations/regions of genes on the Ensembl website do not agree with the location in the vcf file.
For instance, the location for this SNP is 13273, but the annotations are (corresponding ensembl archive version 108):

Agrees: http://oct2022.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000223972;r=1:12010-13670;t=ENST00000450305
Agrees: http://oct2022.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000290825;r=1:11869-14409;t=ENST00000456328
Does not agree: http://oct2022.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000227232;r=1:14404-29570;t=ENST00000488147
Does not agree: http://oct2022.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000278267;r=1:17369-17436;t=ENST00000619216

What am I missing here?
Kind regards,
Eva

**Tags:** vcf, ensembl, identifiers, vep

---

## 1 answers

### Answer by username_1 on 2023-11-06. Score: 2 | Accepted answer

You need to set your expectations clearly instead of just saying "Does not agree". I'm taking a guess here - your statement is that the 2/4 of the gene co-ordinates do not overlap the variant location.

This is because you're viewing just part of the picture - the co-ordinates - and not seeing another important part, which is the kind of effect. For the latter two genes, VEP clearly says the effect is `downstream_gene_variant`, which [Sequence Ontology defines](http://www.sequenceontology.org/browser/current_svn/term/SO:0001632) as "A sequence variant located 3' of a gene."

Putting those two pieces together, the entire picture makes sense. Variants affect different transcripts (of possibly different genes) in different manners. Looking at just 1 of those 2 components will of course make things seem odd.

> **Comments:**
> **username_0**: You are right, it is just overlapping genes. And VEP annotates these, while other variant annotation tools like ANNOVAR do not (just outputs the most deleterious) [ref](https://www.goldenhelix.com/blog/the-sate-of-variant-annotation-a-comparison-of-annovar-snpeff-and-vep/).  
> **username_1**: That’s not true. Both tools can annotate all or most deleterious effects depending on the parameters you use.  
> **username_1**: Just saw the reference post you’d added - that post is wrong. See ANNOVAR documentation- it says “ If the users want to have all functional consequences printed out (rather than just the most important one defined by the precedence above), the --separate argument should be used. In this case, several output lines may be present for each variant, representing several possible functional consequences.”  
> **username_0**: I guess the difference would be the default behavior maybe, but you are right. Sorry for the confusion and thank you for your patience.  

---

