chr8-42770520-C-A

Position:

• chr8-42770520-C-A

Variant summary

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

The ENST00000533810.5(CHRNA6):​c.-158-5316G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 150,380 control chromosomes in the GnomAD database, including 1,694 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 0.14 (1694 hom., cov: 30)
• Consequence: CHRNA6 ENST00000533810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509

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 = 0.209 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.-158-5316G>T		intron_variant		4		ENSP00000434659

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20433 AN: 150314 Hom.: 1691 Cov.: 30

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.00156

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.100

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.136 AC: 20473 AN: 150380 Hom.: 1694 Cov.: 30 AF XY: 0.128 AC XY: 9398 AN XY: 73268

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.00156

Gnomad4 SAS AF: 0.0372

Gnomad4 FIN AF: 0.0548

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.138

Alfa AF: 0.121 Hom.: 2513

Bravo AF: 0.146

Asia WGS AF: 0.0380 AC: 133 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	0.13
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16891620; hg19: chr8-42625663;