Single variant genome position

Help & Support
1

Greetings dear AlphaGenome community,

First of all, I want you all to know that I’m currently an undergraduate biology student, so I hope this question isn’t “dumb” due to the possibility of lack of knowledge in general or bioinformatics…

I’m trying to test the effects of a single variant (SNP) from ClinVar using AlphaGenome, but I noticed something confusing. Usually, to locate a gene, I use the web “Genome Browser”. For example, if you search “HOXA13”, the location is: chr7: 27_194_364 - 27_200_091.

However, if you put the following code in AlphaGenome, you will find another result…

interval = gene_annotation.get_gene_interval(gtf, gene_symbol='HOXA13')

interval

OUTPUT RESULT: Interval(chromosome='chr7', start=27193502, end=27200091, strand='-', name='HOXA13')

The location given from AlphaGenome is a bit different, so I was wondering if I need to write the location as for example in the following script bellow, which location should I use? My SNP variant in ClinVar is located at: chr7: 27_102_230 (GRCh38). Should I use that exact position and assume AlphaGenome will evaluate the exact locus I want?

variant = genome.Variant(
    chromosome='chr7',
    position=27102230,
    reference_bases='A',  # Can differ from the true reference genome base.
    alternate_bases='G',
)

One more question: HOXA13 is transcribed from the minus strand. If ClinVar reports the variant as A>G, should I enter it exactly as A>G, or should I use the plus-strand equivalent (T>C) when creating the Variant object?

Thank you all for your time and help, and again, sorry if my question is a bit basic.

2

Hi There!

Thank for reaching out.

It looks like the location chr7: 27_194_364 - 27_200_091relates to transcript ENST00000649031.1 from HOXA13. get_gene_intervalis extracting the coordinates of the whole HOXA13 gene as opposed to a single transcript.

The position parameter in genome.Variant relates to the forward strand using a 1-based coordinate system to maintain compatibility with common public variant formats (see documentation here), therefore you should enter the variant as is (A>G) without creating a reverse complement.

Kind regards,
Tumi