Genetic variant

rs16969968 a variant in the CHRNA5 gene

rs16969968 is a single-letter difference in the CHRNA5 gene, on chromosome 15. ClinVar, the public archive of variant interpretations, lists it as drug response: linked to how the body handles certain medicines. It has been reported in connection with Lung cancer susceptibility 2 and Smoking as a quantitative trait locus 3, among others. 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 rs16969968 is the catalogue number of one of them, in the CHRNA5 gene. Which letters you carry there — one copy from each parent — is your genotype.

CHRNA5 (cholinergic receptor nicotinic alpha 5 subunit): The protein encoded by this gene is a nicotinic acetylcholine receptor subunit and a member of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. These receptors are thought to be heteropentamers composed of separate but similar subunits. Defects in this gene have been linked to susceptibility to lung cancer type 2 (LNCR2).[provided by RefSeq, Jun 2010]

Gene description from NCBI Gene

Associated with smoking phenotype (p=0.007) based on association study of 2,000 individuals, and fu...

From SNPedia

Why might it matter?

ClinVar records this variant as drug response, meaning linked to how the body handles certain medicines. 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

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 rs16969968, 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?

  1. Find out whether you carry it. Reading about a variant says nothing about you until you know your genotype.
  2. Put it in context. Add your blood results, so the variant can be read against what your body is doing.
  3. Ask questions. Dr. Hemsworth, our AI assistant, can explain this variant and your results in plain English.
  4. 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
rs16969968
Gene
CHRNA5
Position (GRCh38)
chr15:78590582
Variant type
snv
Consequence
missense variant
ClinVar classification
drug response

Genome-wide association studies (15)

TraitRisk alleleOR / betaP-valueStudy
Smoking behaviour (cigarettes smoked per day) A β 0.096 3E-139 PubMed
Lung cancer A OR 0.22 2E-54 PubMed
Fagerstrӧm test for nicotine dependence G OR 0.23 4E-28 PubMed
Chronic obstructive pulmonary disease A OR 1.11 5E-25 PubMed
Small cell lung carcinoma — OR 0.26 1E-23 PubMed
Time to smoke first cigarette in the morning G β 0.07 1E-17 PubMed
Post bronchodilator FEV1/FVC ratio A β 0.017 1E-15 PubMed
Post bronchodilator FEV1 A β 0.078 6E-15 PubMed
Cryptic phenotype that captures alpha-1-antitrypsin deficiency severity A β 0.006 3E-12 PubMed
Pre bronchodilator FEV1/FVC ratio — β 0.017 2E-10 PubMed
Chronic airway obstruction (time to event) x smoking status interaction — — 8E-10 PubMed
Pre bronchodilator FEV1 — β 0.08 2E-9 PubMed
Chronic airway obstruction (time to event) x smoking status interaction — — 6E-9 PubMed
ICD10 Z72.0: Tobacco use — — 2E-7 PubMed
Post bronchodilator FEV1/FVC ratio in COPD A β 0.012 4E-7 PubMed

ClinVar submissions (7)

NM_000745.4(CHRNA5):c.1192G>A (p.Asp398Asn)
· 4 submitters
NM_000745.4(CHRNA5):c.1192G>A (p.Asp398Asn)
· 4 submitters
NM_000745.4(CHRNA5):c.1192G>A (p.Asp398Asn)
· 5 submitters
NM_000745.4(CHRNA5):c.1192G>A (p.Asp398Asn)
· 5 submitters
NM_000745.4(CHRNA5):c.1192G>A (p.Asp398Asn)
· 5 submitters
NM_000745.4(CHRNA5):c.1192G>A (p.Asp398Asn)
· 5 submitters
NM_000745.4(CHRNA5):c.1192G>A (p.Asp398Asn)
· 5 submitters

How common the less frequent letter is

gnomAD ALL
30.8%
1kG AFR
2.3%
1kG ALL
15%
1kG AMR
20.9%
1kG EAS
97.3%
1kG EUR
63.4%
1kG SAS
18.2%

Sources