How can we find disease-associated variants of a Transcript?

Question

[Cyrille]

Hello guys,

Please need help on finding disease variants given a list of Ensembl transcript ids or Transcript sequences. Which database can I use to do such work?

Also, if there is a python API I can work with to do the job. That would be great.

Thank you all.

Answer 1

[Ben_Ensembl]

Hi Cyrille,

If you want to use the Ensembl browser, you can navigate to the 'Variant table' on the transcript tab for your transcript of interest, then filter based on 'Clinical Significance'. E.g:

https://www.ensembl.org/Homo_sapiens/Transcript/Variation_Transcript/Table?db=core;g=ENSG00000147465;r=8:38142700-38150992;t=ENST00000276449

Phenotype associations are not displayed in this table, but you can find out more by clicking on the idividual variant IDs within the table. E.g: https://www.ensembl.org/Homo_sapiens/Variation/Phenotype?db=core;g=ENSG00000147465;r=8:38142700-38150992;t=ENST00000276449;v=rs774615544;vdb=variation;vf=732096370

More information about the clinical significance data available through Ensembl can be found here: https://www.ensembl.org/info/genome/variation/phenotype/phenotype_annotation.html

If you want to retrieve this data programatically, you can use the 'Variation' endpoints of the Ensembl REST API: http://rest.ensembl.org/

[Cyrille]

Thank you Ben.

I have explored the links you sent and indeed the ensembl table contains transcript variants.

I wish to know if all these have a disease associated to them. Or if not, where in the ensembl database can I get annotations whether the variant is associated to a disease or not.

Thank you

[Ben_Ensembl]

No problem, Cyrille.

You can see if a variant has an associated phenotype annotation by looking at the 'Evidence' column in the transcript table for the phenotype icon which is displayed as two overlapping eyes.

The transcript variant table can be filtered to only show variants with a 'clinical significance' annotation and/or phenotype annotation using the blue filter options just above the table itself. You will need to filter against the Clinical significance column and/or the Evidence column.

You can then export the filtered table using the Excel icon in the top right hand corner of the table.

[Cyrille]

Thanks again Ben,

That was very helpful.