Genetic variant
rs12654264 a variant in the HMGCR gene
rs12654264 is a single-letter difference in the HMGCR gene, on chromosome 5. ClinVar, the public archive of variant interpretations, lists it as association: seen more often in people with a condition, which is not the same as causing it. It has been reported in connection with Low density lipoprotein cholesterol level quantitative trait locus 3. Carrying it does not, on its own, mean you have or will develop any condition.
What is this?
Your DNA is a long sequence of four letters. At a few million positions, people commonly differ by a single letter; each of those positions is called a SNP (“snip”), and rs12654264 is the catalogue number of one of them, in the HMGCR gene. Which letters you carry there — one copy from each parent — is your genotype.
HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase): HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis and is regulated via a negative feedback mechanism mediated by sterols and non-sterol metabolites derived from mevalonate, the product of the reaction catalyzed by reductase. Normally in mammalian cells this enzyme is suppressed by cholesterol derived from the internalization and degradation of low density lipoprotein (LDL) via the LDL receptor.
Gene description from NCBI Gene
Genetic variation in 3-hydroxy-3-methylglutaryl CoA reductase modifies the chemopreventive activity ...
From SNPedia
Why might it matter?
ClinVar records this variant as association, meaning seen more often in people with a condition, which is not the same as causing it. A classification describes the variant, not you: what it means for one person depends on their genotype, their family history and often on other genes and circumstances.
Conditions it has been reported with
- Low density lipoprotein cholesterol level quantitative trait locus 3
Listed in ClinVar submissions for this variant. Being listed is a report of an association, not a statement that the variant causes the condition in any given person.
Do I have this variant?
If you have taken a consumer DNA test (23andMe, AncestryDNA and similar), you can download its raw data file and check. Create a free account, upload the file, and this page will show the letters you carry at rs12654264, if your test read this position.
Connect this with your blood results
A gene is a fixed instruction; a blood test shows what your body is doing now. CheckMyBloods reads the two side by side, so a variant can be set against the markers it could plausibly affect.
Blood markers do not diagnose a genetic condition, and a variant does not explain a blood result on its own. Together, with symptoms and family history, they give a clinician context.
What should I do next?
- Find out whether you carry it. Reading about a variant says nothing about you until you know your genotype.
- Put it in context. Add your blood results, so the variant can be read against what your body is doing.
- Ask questions. Dr. Hemsworth, our AI assistant, can explain this variant and your results in plain English.
- Take anything that worries you to a professional. A GP or genetic counsellor can order a confirmatory test and interpret it with your history.
This page is general information drawn from public research databases. It cannot diagnose anything, and it is not a substitute for advice from a doctor or genetic counsellor who knows your history.
Technical details
- dbSNP ID
- rs12654264
- Gene
- HMGCR
- Position (GRCh38)
- chr5:75352777
- Variant type
- snv
- Consequence
- intron variant
- ClinVar classification
- association
Genome-wide association studies (10)
| Trait | Risk allele | OR / beta | P-value | Study |
|---|---|---|---|---|
| LDL cholesterol | T | β 0.1 | 1E-20 | PubMed |
| Metabolite levels | T | OR 2.71 | 1E-20 | PubMed |
| Total cholesterol levels | — | OR 3.23 | 7E-20 | PubMed |
| Triglycerides in small LDL | A | β 0.036 | 2E-19 | PubMed |
| Low density lipoprotein cholesterol levels | — | OR 2.82 | 7E-19 | PubMed |
| Triglycerides in medium LDL | A | β 0.035 | 1E-18 | PubMed |
| Cholesterol esters in very large VLDL | A | β 0.027 | 5E-11 | PubMed |
| Cholesterol | T | OR 2.63 | 1E-9 | PubMed |
| Total cholesterol levels | T | β 0.06 | 3E-7 | PubMed |
| Low density lipoprotein cholesterol levels | — | — | 1E-6 | PubMed |
How common the less frequent letter is
- 1kG AFR
- 31.8%
- 1kG ALL
- 43.6%
- 1kG AMR
- 59.8%
- 1kG EAS
- 49%
- 1kG EUR
- 61%
- 1kG SAS
- 58.9%
Sources
- dbSNP: rs12654264 — the reference record
- ClinVar — clinical interpretations submitted by laboratories
- SNPedia — community-written summaries
- NCBI Gene: HMGCR
- Ensembl: HMGCR
- GWAS Catalog — association studies