How does VEP decide on canonical transcripts and is there a list?

Question

[hagen.klett]

Hi there,

I've used VEP (GRCh38.90) with the option --canonical to annotate my variants from WES and want to focus on canonical transcripts. This gives me a column if the associated transcript is the canonical one.

Now I'd like to retrieve a list of all canonical transcripts as used by VEP and failed to do so. I've tried to get all canonical transcripts following this thread https://groups.google.com/forum/#!topic/biomart-users/skO4zgqzGBA and I've downloaded knownCanonical.txt from UCSC.

However, both approaches have discrepancies to VEP. For example VEP reports ENST00000288602 as the canonical transcript of BRAF, while the output from biomart reports ENST00000496384 and knownCanonical reports ENST00000646891. I would like to go with VEP, so is there a way to obtain such a list from the VEP cache for example?

Any help is greatly appreciated.

Answer 1

[Emily]

Glossary

Canonical transcript
The canonical transcript is used in the gene tree analysis in Ensembl and does not necessarily reflect the most biologically relevant transcript of a gene. For human, the canonical transcript for a gene is set according to the following hierarchy:

1. Longest CCDS translation with no stop codons.

2. If no (1), choose the longest Ensembl/Havana merged translation with no stop codons.

3. If no (2), choose the longest translation with no stop codons.

4. If no translation, choose the longest non-protein-coding transcript.

[hagen.klett]

Thanks Emily, I've found that in the documentation as well. Is there a list of all canonical transcripts or a script on how to create such a list?

[Emily]

It's in the MySQL database and can be accessed via the Perl API. It's not a very meaningful piece of information, which is why we don't make it readily available.

[hagen.klett]

Thanks Emily, I've found that in the documentation as well. Is there a list of all canonical transcripts or a script on how to create such a list?

[lecob]

Hello hagen.klett, I'd like to ask you if you could retrieve the list of VEP canonical transcripts, as suggested by Emily_Ensembl. Unfortunately, I've never used Perl and I couldn't find how to retrieve this list from the link Emily_Ensembl posted. Thank you for your help :)

[soheilshams12]

As follow up to the original question, it seems like the "canonical" transcripts are not necessarily those that have been associated with a disease. Does VEP offer such a list? I believe HGMD has such a list but that requires a commercial license. Are there any other sources for getting such a list?