<div dir="ltr"><br clear="all"><div><div dir="ltr" class="gmail_signature" data-smartmail="gmail_signature"><div dir="ltr"><div dir="ltr"><div>Hello Nakib,</div><div><br></div><div>After double checking, I found that my previous claim was wrong due to incorrect paths being used.</div><div>I have done tests again with 5 old versions of VEP (92.6, 93.5, 94.5, 99.2, 100.4) and 3 different versions of GRCh37 RefSeq cache (92, 99, 100)</div><div>Below are the observations:</div><div><ul><li>Example 1 (10-97192324-A-G, NM_001034954.1:c.182T>C)</li><ul><li>For cache version ≤ 99:</li><ul><li>HGVSp: NP_001030126.1:p.Pro61=</li><li>Consequence: synonymous_variant</li></ul><li>For cache version 100:</li><ul><li>HGVSp: NP_001030126.1:p.Leu61Pro</li><li>Consequence: missense_variant</li></ul></ul><li>Example 2 (4-648595-G-GTGTCTTCTGCTTCTCAGGAAAT, NM_000283.3:c.928-9_940dup)</li><ul><li>For ensembl-vep version ≤ 99:</li><ul><li>HGVSp: NP_000274.2:p.Tyr314CysfsTer50</li><li>Consequence: intron_variant</li></ul><li>For ensembl-vep version = 100:</li><ul><li>HGVSp: -</li><li>Consequence: intron_variant</li></ul></ul><li>Example 3 (14-75483904-T-TCTATGGGAAGAAAGAATAACTTCAATTAGCAATATG, NM_001040108.1:c.4243-36_4243-1dup)</li><ul><li>Fro ensembl-vep version ≤93:</li><ul><li>HGVSp: NP_001035197.1:p.Gln1414_Ile1415insHisIleAlaAsnTerSerTyrSerPhePheProTer</li><li>Consequence: stop_gained,inframe_insertion,splice_region_variant</li></ul><li>For ensembl-vep version ≥94:</li><ul><li>HGVSp: NP_001035197.1:p.Gln1414_Ile1415insHisIleAlaAsnTer</li><li>Consequence: stop_gained,inframe_insertion,splice_region_variant</li></ul></ul></ul></div><div><br></div><div>For example 1, I would assume that the difference is due to the updated RefSeq cache. Therefore, I believe I will inevitably have to reanalyze all the samples with the latest VEP.</div><div>For examples 2 and 3, I believe the differences are due to code change, though I am not not sure which changes would explain the differences.</div><div><br></div><div>Below are the example input file and test commands anyway:</div><div><br></div><div>test_cases.vcf (spaces are tabs):</div></div></div></div></div><blockquote style="margin:0 0 0 40px;border:none;padding:0px"><div><div class="gmail_signature" data-smartmail="gmail_signature"><div><div><div><font face="monospace">##fileformat=VCFv4.1</font></div></div></div></div></div><div><div class="gmail_signature" data-smartmail="gmail_signature"><div><div><font face="monospace">#CHROM POS ID REF ALT QUAL FILTER INFO</font></div></div></div></div><div><div class="gmail_signature" data-smartmail="gmail_signature"><div><div><font face="monospace">10 97192324 example_1 A G . . .</font></div></div></div></div><div><div class="gmail_signature" data-smartmail="gmail_signature"><div><div><font face="monospace">4 648595 example_2 G GTGTCTTCTGCTTCTCAGGAAAT . . .</font></div></div></div></div><div><div class="gmail_signature" data-smartmail="gmail_signature"><div><div><font face="monospace">14 75483904 example_3 T TCTATGGGAAGAAAGAATAACTTCAATTAGCAATATG . . .</font></div></div></div></div></blockquote><div><div dir="ltr" class="gmail_signature" data-smartmail="gmail_signature"><div dir="ltr"><div dir="ltr"><div><br></div><div>Test commands:</div></div></div></div></div><blockquote style="margin:0 0 0 40px;border:none;padding:0px"><div><div class="gmail_signature" data-smartmail="gmail_signature"><div><div><div><font face="monospace">VEP_VERSIONS="92.6 93.5 94.5 99.2 100.4"</font></div></div></div></div></div><div><div class="gmail_signature" data-smartmail="gmail_signature"><div><div><div><font face="monospace">CACHE_VERSIONS="92 99 100"</font></div></div></div></div></div><div><div class="gmail_signature" data-smartmail="gmail_signature"><div><div><div><font face="monospace">for vep in $VEP_VERSIONS; do</font></div></div></div></div></div><div><div class="gmail_signature" data-smartmail="gmail_signature"><div><div><div><font face="monospace"> for cache in $CACHE_VERSIONS; do</font></div></div></div></div></div><div><div class="gmail_signature" data-smartmail="gmail_signature"><div><div><div><font face="monospace"> ./ensembl-vep-release-${vep}/vep --cache --offline --force_overwrite --tab --format vcf --no_stats --no_headers \</font></div></div></div></div></div><div><div class="gmail_signature" data-smartmail="gmail_signature"><div><div><div><font face="monospace"> </font><span style="font-family:monospace">--refseq --exclude_predicted </span><span style="font-family:monospace">--hgvs --total_length --biotype --canonical --pick --pick_order length,canonical,biotype,rank \</span></div></div></div></div></div><div><div class="gmail_signature" data-smartmail="gmail_signature"><div><div><div><font face="monospace"> --fields Uploaded_variation,CANONICAL,BIOTYPE,Consequence,CDS_position,HGVSc,HGVSp,PICK \</font></div></div></div></div></div><div><div class="gmail_signature" data-smartmail="gmail_signature"><div><div><div><font face="monospace"> --fasta data/Homo_sapiens.GRCh37.75.dna.primary_assembly.fa --dir data --cache_version ${cache} \</font></div></div></div></div></div><div><div class="gmail_signature" data-smartmail="gmail_signature"><div><div><div><font face="monospace"> -i test_cases.vcf -o test_cases_vep_${vep}_${cache}.txt</font></div></div></div></div></div><div><div class="gmail_signature" data-smartmail="gmail_signature"><div><div><div><font face="monospace"> done</font></div></div></div></div></div><div><div class="gmail_signature" data-smartmail="gmail_signature"><div><div><div><font face="monospace">done</font></div></div></div></div></div></blockquote><div><div dir="ltr" class="gmail_signature" data-smartmail="gmail_signature"><div dir="ltr"><div dir="ltr"><div><br></div><div dir="ltr"><span>Regards,<br>Wallace Ko</span></div></div></div></div></div><br></div><br><div class="gmail_quote"><div dir="ltr" class="gmail_attr">On Fri, Jan 21, 2022 at 11:23 PM Syed Hossain <<a href="mailto:snhossain@ebi.ac.uk">snhossain@ebi.ac.uk</a>> wrote:<br></div><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex">Hello Wallace,<br>
<br>
Thank you for reporting this issue. But, unfortunately, we were unable <br>
to reproduce it.<br>
<br>
For our case VEP v99 is also giving the same output as what you get for <br>
VEP v100 (i.e - HGVSc: NM_001034954.1:c.182T>C --> HGVSp: <br>
NP_001030126.1:p.Leu61Pro).<br>
<br>
Can you kindly share the full command you are using and (if possible) <br>
the input files.<br>
<br>
Best regards,<br>
Nakib<br>
<br>
On 2022-01-20 13:02:47 +0800, Wallace Ko wrote:<br>
> Hello Ensembl Team,<br>
> <br>
> During re-evaluation of some old samples, we found that VEP v99 and <br>
> v100<br>
> give the same HGVSc, but different annotation, including consequence <br>
> and<br>
> HGVSp, e.g.:<br>
> <br>
> 1. HGVSc: NM_001034954.1:c.182T>C<br>
> - v99:<br>
> - HGVSp: NP_001030126.1:p.Pro61=<br>
> - Consequence: synonymous_variant<br>
> - v100:<br>
> - HGVSp: NP_001030126.1:p.Leu61Pro<br>
> - Consequence: missense_variant<br>
> 2. HGVSc: NM_000283.3:c.928-9_940dup<br>
> - v99 HGVSp: NP_000274.2:p.Tyr314CysfsTer50<br>
> - v100 HGVSp: -<br>
> 3. HGVSc: NM_001040108.1:c.4243-36_4243-1dup<br>
> - v99 HGVSp:<br>
> <br>
> NP_001035197.1:p.Gln1414_Ile1415insHisIleAlaAsnTerSerTyrSerPhePheProTer<br>
> - v100 HGVSp: NP_001035197.1:p.Gln1414_Ile1415insHisIleAlaAsnTer<br>
> <br>
> I tried using offline VEP v100 with v99 cache and vice versa. VEP v100<br>
> produces the new results regardless of the cache being used. So it <br>
> should<br>
> be due to code change instead of data update.<br>
> <br>
> The change is sort of significant but there seem no relevant details in <br>
> the<br>
> release descriptions (<br>
> <a href="https://github.com/Ensembl/ensembl-vep/releases?q=release%2F100" rel="noreferrer" target="_blank">https://github.com/Ensembl/ensembl-vep/releases?q=release%2F100</a>) or the<br>
> mail list about the change.<br>
> <br>
> I wonder what causes such changes and if there is a scope or pattern on <br>
> the<br>
> changes. Otherwise, we may need to re-analyze all results from VEP v99 <br>
> or<br>
> older.<br>
> <br>
> Thank you.<br>
> <br>
> Regards,<br>
> Wallace Ko<br>
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