GRCh38 query - offline environment

[lgrob]

Dear all,

Thanks for developing civicpy. We need to query CIViC for variant information using GRCh38 coordinates, but due to data protection requirements, all processing must take place in a fully offline environment.

Currently, our attempts to use CIViC offline are hindered because the package still tries to contact reg.genome.network. Do you have any advice or best practices for completely offline querying of CIViC using civicpy — ideally with GRCh38 support? If an entirely offline solution is only available for GRCh37, would it be feasible to perform a local liftover as a workaround?

Thank you in advance.

Best,
Linda

Querying CIViC for chr1:874297-874297 C>T (GRCh38) WARNING:urllib3.connectionpool:Retrying (Retry(total=4, connect=5, read=4, redirect=None, status=None)) after connection broken by 'ConnectionResetError(104, 'Connection reset by peer')': /allele?hgvs=NC_000001.11%3Ag.874297C%3ET WARNING:urllib3.connectionpool:Retrying (Retry(total=3, connect=5, read=3, redirect=None, status=None)) after connection broken by 'ConnectionResetError(104, 'Connection reset by peer')': /allele?hgvs=NC_000001.11%3Ag.874297C%3ET WARNING:urllib3.connectionpool:Retrying (Retry(total=2, connect=5, read=2, redirect=None, status=None)) after connection broken by 'ConnectionResetError(104, 'Connection reset by peer')': /allele?hgvs=NC_000001.11%3Ag.874297C%3ET WARNING:urllib3.connectionpool:Retrying (Retry(total=1, connect=5, read=1, redirect=None, status=None)) after connection broken by 'ConnectionResetError(104, 'Connection reset by peer')': /allele?hgvs=NC_000001.11%3Ag.874297C%3ET WARNING:urllib3.connectionpool:Retrying (Retry(total=0, connect=5, read=0, redirect=None, status=None)) after connection broken by 'ConnectionResetError(104, 'Connection reset by peer')': /allele?hgvs=NC_000001.11%3Ag.874297C%3ET Error querying variant chr1:874297 C>T: HTTPConnectionPool(host='reg.genome.network', port=80): Max retries exceeded with url: /allele?hgvs=NC_000001.11%3Ag.874297C%3ET (Caused by ProtocolError('Connection aborted.', ConnectionResetError(104, 'Connection reset by peer')))

[VBabih]

That is a great request. Currently, my team is facing the same issue. I hope they can give us a solution!

[jsstevenson]

From eyeballing the code - it looks like coordinate-based searches currently hit the clingen allele registry because they need to convert coordinates into an allele registry ID, and then search variants by that ID.

It appears this does NOT happen with HGVS expressions, so if it's not too difficult to make that conversion on your end, that could be a bandaid solution