8-42763247-C-T

Position:

• chr8-42763247-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.219+1818G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,132 control chromosomes in the GnomAD database, including 3,139 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 0.16 (3139 hom., cov: 32)
• Consequence: CHRNA6 NM_004198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA6	NM_004198.3	c.219+1818G>A		intron_variant		ENST00000276410.7	NP_004189.1
CHRNA6	NM_001199279.1	c.219+1818G>A		intron_variant			NP_001186208.1
CHRNA6	XM_047422396.1	c.219+1818G>A		intron_variant			XP_047278352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA6	ENST00000276410.7	c.219+1818G>A		intron_variant		1	NM_004198.3	ENSP00000276410.3
CHRNA6	ENST00000534622.5	c.219+1818G>A		intron_variant		2		ENSP00000433871.1
CHRNA6	ENST00000533810.5	c.-19+1818G>A		intron_variant		4		ENSP00000434659.1
CHRNA6	ENST00000530869.1	n.421+1818G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24460 AN: 152014 Hom.: 3136 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0945

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0563

Gnomad OTH AF: 0.159

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.161 AC: 24500 AN: 152132 Hom.: 3139 Cov.: 32 AF XY: 0.164 AC XY: 12185 AN XY: 74378

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.0945

Gnomad4 NFE AF: 0.0563

Gnomad4 OTH AF: 0.161

Alfa AF: 0.0862 Hom.: 1065

Bravo AF: 0.178

Asia WGS AF: 0.217 AC: 753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.57

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: rs10109429; hg19: chr8-42618390;