Exome Aggregation Consortium (ExAC) dataset

Question

[kiruphagaran]

Hi all,

I have some doubts regarding the EXAC (Exome Aggregation Consortium) dataset. For a gene, if we click a variant it gives a detailed description about that particular variant. What does non coding transcript exon under Annotations mean?. And when you move the cursor to the allele number it shows total number of called genotypes. Does it refer to the depth to which it is sequenced? and what does site quality metrics mean?. Thank you.

Answer 1

[WouterDeCoster]

Could you give an example in which you see this non coding transcript exon annotation?

I don't completely understand your description, but the number of called genotypes likely refers to the number of samples.

Changed this thread from 'forum' to 'question'.

Answer 2

[kiruphagaran]

Hi, WouterDeCoster thank you so much for your response. For example i have given a link to a particular variant and under Annotations on the right side it is mentioned non coding transcript exon.

http://exac.broadinstitute.org/variant/20-36760783-C-T

[WouterDeCoster]

Please use the comment function to keep replies logically together.

As you can see, that variant is localized in 4 transcripts. The annotation is a missense variant for 3 transcripts of that gene and the fourth transcript is a noncoding transcript (i.e. it has no known protein product). As such the annotation is for the fourth that this variant is localized in an exon of a non coding transcript. You can see this gene in Ensembl: http://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000198959;r=20:38128461-38133760;t=ENST00000469269 And indeed, there are both coding and non-coding transcripts.

[kiruphagaran]

Thank you so much. Now its clear for me. If you dont mind I have one more query. Under Population Frequencies there is allele count and allele number. But for some populations the allele count is 0 but there is allele number. Does it mean that particular variant is absent in that population. For example in this link below there are 2 carriers in European and 1 in African. Although in other populations its 0 carriers there are allele numbers.

http://exac.broadinstitute.org/variant/20-36758625-G-A

[WouterDeCoster]

The allele count is the number of times that variant was found, the allele number is the number of alleles that have been sequenced. So for your example variant: In the European (Non-Finnish) population the variant is found twice out of 62648 alleles (and thus 31324 individuals). In the East Asian population the variant is not found (0) out of 8084 alleles (and thus 4042 individuals).

[kiruphagaran]

Do you mean that out of 31324 sequenced European (Non-Finnish) individuals only 2 had this variant?

[WouterDeCoster]

Yes indeed. See also the very low allele frequency in the last column (3.192e-05).

[kiruphagaran]

Thank you so much for your time.

Answer 3

[kiruphagaran]

Hi WouterDeCoster,

I have a doubt regarding the ExAC database about the allele frequency. For some variants the allele frequency is over 50 %. How to interpret it. Does it mean that it is more frequent than the wild-type?

[WouterDeCoster]

"Wild-type" isn't the correct term in (human) population genetics. I'd say every one of us is equally wild regardless of presence or absence of rare variants. The correct term and way of viewing this would be "reference allele", meaning the allele which was found when constructing the human reference genome (using a few donors - not one sample). Therefore, it's very well possible (and indeed happens as you see) that the reference allele isn't the major allele.

[kiruphagaran]

Hi, Thank you. One more question. Is there a difference between minor allele frequency and allele frequency?