rs2304297

Positions:

• chr8-42753056-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004198.3(CHRNA6):​c.*123C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 828,322 control chromosomes in the GnomAD database, including 40,149 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (15643 hom., cov: 32)
  • Exomes 𝑓: 0.25 (24506 hom.)
• Consequence: CHRNA6 NM_004198.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510

Genes affected

CHRNA6 (HGNC:15963): (cholinergic receptor nicotinic alpha 6 subunit) This gene encodes an alpha subunit of neuronal nicotinic acetylcholine receptors. These receptors consist of five subunits and function as ion channels involved in neurotransmission. The encoded protein is a subunit of neuronal nicotinic acetylcholine receptors that mediate dopaminergic neurotransmission and are activated by acetylcholine and exogenous nicotine. Alternatively spliced transcript variants have been observed for this gene. Single nucleotide polymorphisms in this gene have been associated with both nicotine and alcohol dependence. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA6	NM_004198.3	c.*123C>G		3_prime_UTR_variant	6/6	ENST00000276410.7
CHRNA6	NM_001199279.1	c.*123C>G		3_prime_UTR_variant	5/5
CHRNA6	XM_047422396.1	c.*123C>G		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA6	ENST00000276410.7	c.*123C>G		3_prime_UTR_variant	6/6	1	NM_004198.3	P1
CHRNA6	ENST00000534622.5	c.*123C>G		3_prime_UTR_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58312 AN: 151956 Hom.: 15596 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.353

GnomAD4 exome AF: 0.253 AC: 171043 AN: 676248 Hom.: 24506 Cov.: 9 AF XY: 0.254 AC XY: 89803 AN XY: 353598

Gnomad4 AFR exome AF: 0.780

Gnomad4 AMR exome AF: 0.264

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.206

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.384 AC: 58415 AN: 152074 Hom.: 15643 Cov.: 32 AF XY: 0.378 AC XY: 28104 AN XY: 74356

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.353

Alfa AF: 0.319 Hom.: 1382

Bravo AF: 0.408

Asia WGS AF: 0.309 AC: 1076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2304297; hg19: chr8-42608199; COSMIC: COSV52381606; COSMIC: COSV52381606;