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Hi Svein,<br>
<br>
In Ensembl, our annotation is based on the reference genome but
RefSeq transcripts can differ from the reference which causes
problems like this in a occasional cases. <br>
In this instance, the reference has a single base deletion with
respect to the RefSeq transcript. The absense of the base in the
reference has caused the Ensembl transcript to have a 2 base intron
within what is a contiguous exon in ReSeq - this accounts for the 3
base difference between the transcripts. The RefSeq/reference
missmatch also causes the problems you observe for the RefSeq
analysis.<br>
<br>
If you look at position 3124 it in the alignment between the two
transcripts, you can see the Ensembl transcript has a 3 base
deletion with respect to the RefSeq transcript:<br>
<br>
<a class="moz-txt-link-freetext" href="http://grch37.ensembl.org/Homo_sapiens/Transcript/Similarity/Align?db=core;extdb=refseq_mrna;g=ENSG00000090006;r=19:41099072-41135725;sequence=NM_003573.2;t=ENST00000204005">http://grch37.ensembl.org/Homo_sapiens/Transcript/Similarity/Align?db=core;extdb=refseq_mrna;g=ENSG00000090006;r=19:41099072-41135725;sequence=NM_003573.2;t=ENST00000204005</a><br>
<br>
If you look at Intron 24-25 on the Exon view you can see the extra
intron this introduces:<br>
<br>
<a class="moz-txt-link-freetext" href="http://grch37.ensembl.org/Homo_sapiens/Transcript/Exons?db=core;extdb=refseq_mrna;g=ENSG00000090006;r=19:41099072-41135725;sequence=NM_003573.2;t=ENST00000204005">http://grch37.ensembl.org/Homo_sapiens/Transcript/Exons?db=core;extdb=refseq_mrna;g=ENSG00000090006;r=19:41099072-41135725;sequence=NM_003573.2;t=ENST00000204005</a><br>
<br>
The GRCh37 site uses an old gene set, but for more recent sets we
hold information on when the RefSeq transcript differs from the
Ensembl transcript and report such discrepancies with command line
VEP. We are seeking to resolve this problem.<br>
<br>
Best wishes,<br>
<br>
Sarah<br>
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<div class="moz-cite-prefix">On 02/12/2015 11:55, Svein Tore Koksrud
Seljebotn wrote:<br>
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<blockquote cite="mid:565EDC41.9040600@medisin.uio.no" type="cite">
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Hi,<br>
<br>
we encountered one variant that gives a bit confusing annotation
output from VEP (GRCh37, release 82).<br>
<br>
The variant is: 19:41133005 G>A (rs200607327).<br>
<br>
If it's still available, an online VEP annotation can be found
here: <a moz-do-not-send="true" class="moz-txt-link-freetext"
href="http://grch37.ensembl.org/Homo_sapiens/Tools/VEP/Results?db=core;tl=1Vp8p7UidQSVCQfB-1297423">http://grch37.ensembl.org/Homo_sapiens/Tools/VEP/Results?db=core;tl=1Vp8p7UidQSVCQfB-1297423</a>
.<br>
<br>
<br>
We use Refseq transcript output for <span style="color:black">NM_003573.2,</span>
and got the following:<br>
<br>
<span style="color:black">NM_003573.2:c.4200G>A |</span><span
style="color:black"> NP_003564.2:p.Met1400Ile | ATG/ATA<br>
<br>
For the corresponding Ensembl transcript </span><span
style="color:black"><span style="color:black">ENST00000204005 </span>[1],
we get the following:<br>
<br>
ENST00000204005.9:c.4198G>A | ENSP00000204005.9:p.Gly1400Arg
| GGG/AGG<br>
<br>
In dbSNP and other databases, the correct cDNA position for the
RefSeq transcript for this variant is 4201, not 4200.<br>
<br>
So I have two questions:<br>
<br>
1. Why is there a three base difference between the two
transcripts (4201 vs 4198)?<br>
<br>
2. Is there something going wrong in the calculation of the
RefSeq data? Note the frameshift for the codons, resulting in
wrong protein as well.<br>
<br>
<br>
Best regards,<br>
Svein Tore Koksrud Seljebotn<br>
<br>
<br>
[1]
<a moz-do-not-send="true" class="moz-txt-link-freetext"
href="http://grch37.ensembl.org/Homo_sapiens/Transcript/Summary?db=core;g=ENSG00000090006;r=19:41099072-41135725;t=ENST00000204005;tl=1Vp8p7UidQSVCQfB-1297423">http://grch37.ensembl.org/Homo_sapiens/Transcript/Summary?db=core;g=ENSG00000090006;r=19:41099072-41135725;t=ENST00000204005;tl=1Vp8p7UidQSVCQfB-1297423</a><br>
</span> <br>
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