rs7828365

chr8-42774171-C-T

Variant summary

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

The ENST00000533810.5(CHRNA6):c.-158-8967G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,240 control chromosomes in the GnomAD database, including 1,621 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 0.13 (1621 hom., cov: 32)
• Consequence: CHRNA6 ENST00000533810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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 = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA6	ENST00000533810.5	c.-158-8967G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20384 AN: 152122 Hom.: 1620 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0387

Gnomad FIN AF: 0.0569

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.134 AC: 20401 AN: 152240 Hom.: 1621 Cov.: 32 AF XY: 0.126 AC XY: 9389 AN XY: 74438

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0385

Gnomad4 FIN AF: 0.0569

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.134

Alfa AF: 0.127 Hom.: 168

Bravo AF: 0.142

Asia WGS AF: 0.0360 AC: 127 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	0.0080
Dann	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7828365; hg19: chr8-42629314;