8-42763247-C-T

Variant names:

• chr8-42763247-C-T
• rs10109429
• NM_004198.3:c.219+1818G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004198.3(CHRNA6):​c.219+1818G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,132 control chromosomes in the GnomAD database, including 3,139 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 0.16 (3139 hom., cov: 32)
• Consequence: CHRNA6 NM_004198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004198.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA6	NM_004198.3	MANE Select	c.219+1818G>A		intron	N/A	NP_004189.1
	CHRNA6	NM_001199279.1		c.219+1818G>A		intron	N/A	NP_001186208.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA6	ENST00000276410.7	TSL:1 MANE Select	c.219+1818G>A		intron	N/A	ENSP00000276410.3
	CHRNA6	ENST00000534622.5	TSL:2	c.219+1818G>A		intron	N/A	ENSP00000433871.1
	CHRNA6	ENST00000533810.5	TSL:4	c.-19+1818G>A		intron	N/A	ENSP00000434659.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24460 AN: 152014 Hom.: 3136 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0945

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0563

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.161 AC: 24500 AN: 152132 Hom.: 3139 Cov.: 32 AF XY: 0.164 AC XY: 12185 AN XY: 74378

African (AFR) AF: 0.346 AC: 14343 AN: 41468

American (AMR) AF: 0.176 AC: 2689 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3472

East Asian (EAS) AF: 0.211 AC: 1091 AN: 5168

South Asian (SAS) AF: 0.161 AC: 776 AN: 4824

European-Finnish (FIN) AF: 0.0945 AC: 1002 AN: 10606

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0563 AC: 3829 AN: 68008

Other (OTH) AF: 0.161 AC: 340 AN: 2106

Alfa AF: 0.0983 Hom.: 1783

Bravo AF: 0.178

Asia WGS AF: 0.217 AC: 753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.57
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10109429; hg19: chr8-42618390;