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VEP, dbNSFP, Offline Mode, Cache version

Hi Team,

I have a question regarding correct usage of VEP and dbNSFP ... Please help with your valuable insights !!!

I'm using dbNSFP plugin with VEP tool ...

content from dbNSFP read file ...

dbNSFP version 4.2a

Release: April 6, 2021

Major sources: Variant determination:

Gencode release 29/Ensembl 94, released October, 2018 (hg38)

As you can see it says that this version is based on Ensembl 94

VEP tool site for the dbNSFP plugin says ...

"Note that transcript sequences referred to in dbNSFP may be out of sync with those in the latest release of Ensembl; this may lead to discrepancies with scores retrieved from other sources."

Does this mean that when I'm using VEP tool with version as 103, or latest, in offline mode I should get the cache with version as 94 ( that matches the version from which the dbNSFP was derived)?

or can I use the latest version of VEP cache ?

Please help Team !!!

annotation vep dbnsfp ensembl
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updated by Emily Emily • written by nobody • nobody

1 answer

Always use the latest cache. The note with dbNSFP just means that if you ran any of dbNSFP algorithms right now you might get slightly different scores than what you'd pull out with the VEP because they were calculated using a different transcript database.

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written by Emily Emily

Thanks Madame for kind response ... one tangential question ... do I need to provide fasta file ( or download fasta file) or using cache in itself sufficient ? I have been using just the cache and don't pass fasta file at all ... just want to check from expert like yourself if that is fine ...

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written by nobody • nobody

There are certain options, such as HGVS in the output, which require a FASTA file. If options need FASTA, this is stated in the documentation. If you don't use these options, you can just run the VEP without FASTA. If you do pick one of these options and you don't have a local FASTA, the VEP will need to connect to our database.

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written by Emily Emily

Thanks Madame ... yes I don't use the HGVS ... and if fasta file is not present and internet connection is not there ... VEP would fail ? basically vep would let me know if fasta file is required rather than silently dumping "wrong" information ?

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written by nobody • nobody

It will tell you.

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written by Emily Emily

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