gnoMAD specific mutation allele position in gnoMAD

Question

[dshdixit]

I have a specific mutation for the CFTR gene but can't find a way to find that position in order to pull out on gnoMAD as they might have specific annotation for it. For example the mutation i am working on c.164+3083C>G(intron 2) in CFTR gene at position 53298. How can i find it in gnoMAD? Sorry if its easy and asking this question as i am new to the area and trying to learn. Thank you so much in advance!

Answer 1

[finswimmer]

Hello,

you have to find out the genomic location of the variant. Than you can use this position to search in gnomad.

You can find the position using ensembl's vep (7:117507446). You search will guide you to this result.

fin swimmer

[dshdixit]

Thank you so much! Its really helpful to understand the way you explained. Could you kindly explain that how did you find out genomic location for this mutation?

[finswimmer]

Hello again,

in ensembl's vep you can create a new job. In the "Input Data" section, you can write your gene of interest and the hgvs description, in your case: CFTR:c.164+3083C>G. Click "Run" and wait. Once the job is finished, click "View Result" and you will find the position in the "Location" column.

Be aware that only giving a gene name and a hgvs description can be ambiguous. It is possible that this matches to different transcripts and thus leading to different genomic location.

One more pitfall: Take care of which reference genome you are using. The linked ensemble uses hg38. So whenever you are looking in a different source for the genomic position make sure, this source also uses hg38. In case of the gnomAD website, make sure you are using v3. Because v2 is based on the very old and outdated hg19.

fin swimmer

[dshdixit]

Thank you so much for stepwise explaination. But when i put in vep this mutation c.164+3083C>G(intron 2) into this format CFTR:c.164+3083C>G. how should i ensure correct annotation, and when i am copying another mutation by copying and pasting from my excel file for other mutation c.53+2664G>A(intron 1) in this format in vep search as you instructed, it doesn't work. Is there a specific annotation i should follow. Could you please help me understand if i am missing something.Really appreciate your help on it, its helping me to understand the sensitivity of it.

[finswimmer]

But when i put in vep this mutation c.164+3083C>G(intron 2) into this format CFTR:c.164+3083C>G. how should i ensure correct annotation

If you have luck (and in most of the cases you will) you will only get one position and then you can be sure. Otherwise it is absolutely necessary to know the transcript you are talking about. You can find it in the feature column of the result table or you can use it in the input instead of the gene name

and when i am copying another mutation by copying and pasting from my excel file for other mutation c.53+2664G>A(intron 1) in this format in vep search as you instructed, it doesn't work.

Make sure you write CFTR in upper case. The search is case sensitiv. Also don't include (intron 1).

As a general advice for working with variants:

• know the reference genome you use (it should be hg38)
• know the transcript and version you use

I'm very happy to see a hgvs description for a CFTR variant and not something like ΔF508 :)

[dshdixit]

Yes no more just ΔF508 as its so much beyond it :) Thank you so much! Its very insightful but i did came across a variant where vep gave me correct location of that hgvs description while when using that location in gnomad its not correlating to same hgvs description. For example- c.53+14433G>A(intron1). Do you think its something wrong from end or i need to address it by gathering other information? Thank you once again for all your help.

[dshdixit]

Thank you so much! Is there also a way where if can SEARCH or pull information on synonymous and non synonymous or non coding for the specific SNV in gnomad?