8-42774752-C-T

Position:

• chr8-42774752-C-T

Variant summary

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

The ENST00000533810.5(CHRNA6):​c.-158-9548G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,110 control chromosomes in the GnomAD database, including 15,823 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 0.39 (15823 hom., cov: 32)
• Consequence: CHRNA6 ENST00000533810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA6	ENST00000533810.5	c.-158-9548G>A		intron_variant		4		ENSP00000434659

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58570 AN: 151992 Hom.: 15777 Cov.: 32

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.386 AC: 58673 AN: 152110 Hom.: 15823 Cov.: 32 AF XY: 0.380 AC XY: 28252 AN XY: 74364

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.364

Alfa AF: 0.235 Hom.: 7802

Bravo AF: 0.414

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.12
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10107450; hg19: chr8-42629895;