8-42760417-C-T

Position:

• chr8-42760417-C-T

Variant summary

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

The ENST00000276410.7(CHRNA6):​c.220-1304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 151,988 control chromosomes in the GnomAD database, including 638 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 0.079 (638 hom., cov: 33)
• Consequence: CHRNA6 ENST00000276410.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA6	NM_004198.3	c.220-1304G>A		intron_variant		ENST00000276410.7	NP_004189.1
CHRNA6	NM_001199279.1	c.220-3380G>A		intron_variant			NP_001186208.1
CHRNA6	XM_047422396.1	c.220-1304G>A		intron_variant			XP_047278352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA6	ENST00000276410.7	c.220-1304G>A		intron_variant		1	NM_004198.3	ENSP00000276410	P1
CHRNA6	ENST00000533810.5	c.-18-1304G>A		intron_variant		4		ENSP00000434659
CHRNA6	ENST00000534622.5	c.220-3380G>A		intron_variant		2		ENSP00000433871
CHRNA6	ENST00000530869.1	n.422-1013G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0788 AC: 11969 AN: 151870 Hom.: 640 Cov.: 33

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.0571

Gnomad FIN AF: 0.0814

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0877

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

GnomAD4 genome AF: 0.0787 AC: 11961 AN: 151988 Hom.: 638 Cov.: 33 AF XY: 0.0755 AC XY: 5607 AN XY: 74282

Gnomad4 AFR AF: 0.0215

Gnomad4 AMR AF: 0.0710

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.00271

Gnomad4 SAS AF: 0.0565

Gnomad4 FIN AF: 0.0814

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.0868

Alfa AF: 0.104 Hom.: 378

Bravo AF: 0.0763

Asia WGS AF: 0.0230 AC: 78 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.41

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: rs17621710; hg19: chr8-42615560;