Some genes are read in the reverse direction, and as a result SNPs are sometimes reported reversed. This happens quite often, as 23andMe will report genotypes on the minus, while SNPedia and dbSNP tend to only report genotypes relative to the plus strand. Making it even more confusing, occasionally snps are flipped between genome versions (ie rs17602729).
Each rs# in SNPedia has a field along the right side called 'Orientation.
If the value is 'minus' you need to change:
This leads to some ambiguous flips.
When needed, Promethease correctly flips genotypes from 23andMe's minus orientation into SNPedia's plus orientation.
discussion at reddit
Excerpt from a real email exchange
I noticed that there are errors in my report. SNP rs1056836 was flagged by Genetic Genie as abnormal (GG) came back as normal (CC) on your report. I confirmed that the GG is correct in my raw data on 23andMe. Also, rs651852 is TT in my raw data and AA on my Promethease report. This is just in searching 4 SNPs that came back abnormally. Do you have any insight on this?
- This is due to orientation issues. SNPedia and Promethease are more correct than any other source that you have seen.
- I'm really new to all of this, and I'm not quite understanding. Are you saying that the alleles reported don't matter in these cases and that the interpretation of "normal" by Promethease is more correct than Genetic Genie's interpretation as "abnormal"?
- The alleles matter, but you need to take orientation into account. Promethease goes to great lengths to do this; other sites don't.
What letters to write after the rs number
We trust dbSNP because they are the ones who assigned the rs#.
you can see that they call rs651852 as RefSNP Alleles: A/G (REV)
other sources such as 23andMe report it as C or T
This is a known issue with the notation we all use
SNPedia can't fix it, but we can try to make the positions prone to confusion obvious. This is why SNPedia and Promethease both show 'Orientation minus' quite prominently.
Perhaps it isn't yet obvious enough, but the general problem is that this often isn't made visible by other sources, and when it is available there is no consistency about terminology.
How to interpret the consequences of the genotype you have (regardless of how it is written)
for rs1056836 there are 3 possible genotypes. In SNPedia's orientation they can be written as
- (C;C) this is found in 33% of caucasians
- (C;G) this is found in 43% of caucasians
- (G;G) this is found in 23% of caucasians
What is normal? Well the most common genotype is (C;G). The C allele is a bit more common than the G, so technically the (G;G) could be considered a rare, but it's found in 23% of people. Flagging it as something rare and bad seems unjustified. SNPedia has more than 50 papers which talk about this SNP, and there is no clear consensus of any significant effect.
As for rs651852, your genotype is found in ~15% of caucasians. There are hardly any papers, and no reliable conclusions that can be drawn.
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