8-42780156-A-G

Position:

• chr8-42780156-A-G

Variant summary

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

The ENST00000533810.5(CHRNA6):​c.-158-14952T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,174 control chromosomes in the GnomAD database, including 3,445 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 0.15 (3445 hom., cov: 32)
• Consequence: CHRNA6 ENST00000533810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118

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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 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.-158-14952T>C		intron_variant		4		ENSP00000434659.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23409 AN: 152056 Hom.: 3439 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0355

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.154 AC: 23454 AN: 152174 Hom.: 3445 Cov.: 32 AF XY: 0.155 AC XY: 11561 AN XY: 74414

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.0793

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.0418

Gnomad4 NFE AF: 0.0355

Gnomad4 OTH AF: 0.160

Alfa AF: 0.0803 Hom.: 263

Bravo AF: 0.177

Asia WGS AF: 0.213 AC: 739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.3
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6474419; hg19: chr8-42635299;