rs7812298

Positions:

• chr8-42753436-C-T

Variant summary

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

The NM_004198.3(CHRNA6):​c.1354-126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 872,060 control chromosomes in the GnomAD database, including 33,809 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 0.36 (13881 hom., cov: 32)
  • Exomes 𝑓: 0.22 (19928 hom.)
• Consequence: CHRNA6 NM_004198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA6	NM_004198.3	c.1354-126G>A		intron_variant		ENST00000276410.7	NP_004189.1
CHRNA6	NM_001199279.1	c.1309-126G>A		intron_variant			NP_001186208.1
CHRNA6	XM_047422396.1	c.1354-126G>A		intron_variant			XP_047278352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA6	ENST00000276410.7	c.1354-126G>A		intron_variant		1	NM_004198.3	ENSP00000276410.3
CHRNA6	ENST00000534622.5	c.1309-126G>A		intron_variant		2		ENSP00000433871.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53977 AN: 151980 Hom.: 13832 Cov.: 32

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.219 AC: 157324 AN: 719962 Hom.: 19928 AF XY: 0.216 AC XY: 82604 AN XY: 382100

Gnomad4 AFR exome AF: 0.739

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.356 AC: 54086 AN: 152098 Hom.: 13881 Cov.: 32 AF XY: 0.349 AC XY: 25969 AN XY: 74360

Gnomad4 AFR AF: 0.730

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.324

Alfa AF: 0.297 Hom.: 1170

Bravo AF: 0.380

Asia WGS AF: 0.270 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.35
DANN	Benign	0.43

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: rs7812298; hg19: chr8-42608579; COSMIC: COSV52379762; COSMIC: COSV52379762;