A confusing result

[Eduardo-Auer]

Hi, I am using Exomiser cli (version 13.2.1) with database version 2302 and in the hg38 reference genome. I analyzed using Exomiser and found an unusual result for the first variant:

This variant has a frameshift consequence according to varsome:

I need help to clarify this result. Is there a way to correct it?

[julesjacobsen]

Looks like VarSome chose ENST00000358450.8 and Jannovar chose ENST00000286063.11. ENST00000286063.11 is the MANE select transcript, but it's annotated as intergenic as the variant lies downstream of this. The underlying issue being that the 2302_hg38_transcripts_ensembl.ser database must be lacking any of the other GENCODE transcripts. Could you try re-running this with an earlier version of the hg38 data.

[Eduardo-Auer]

Looks like VarSome chose ENST00000358450.8 and Jannovar chose ENST00000286063.11. ENST00000286063.11 is the MANE select transcript, but it's annotated as intergenic as the variant lies downstream of this. The underlying issue being that the 2302_hg38_transcripts_ensembl.ser database must be lacking any of the other GENCODE transcripts. Could you try re-running this with an earlier version of the hg38 data.

Hello, I used Exomiser cli (version 13.2.1) with database version 2209 ( with phenotype) and in the hg38 reference genome. Here is the result:

[damiansm]

The latest db (based on popular request) just has the MANE select and MANE clinical transcripts and overall this improves performance by getting rid of false positives. Looking at https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000128655;r=2:177623244-178108339 the old ENST00000358450.8 Gencode-basic transcript was not selected by MANE. Wondering if there is a need to make this transcript a MANE-clinical one in future Ensembl releases or is this a false Clinvar LP call?