rs2217732

Variant names:

• chr8-42763303-A-G
• rs2217732
• NM_004198.3:c.219+1762T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-42763303-A-G
• chr8-42763303-A-T

Variant summary

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

The ENST00000276410.7(CHRNA6):​c.219+1762T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,122 control chromosomes in the GnomAD database, including 14,088 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 0.36 (14088 hom., cov: 32)
• Consequence: CHRNA6 ENST00000276410.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000276410.7. 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+1762T>C		intron	N/A	NP_004189.1
	CHRNA6	NM_001199279.1		c.219+1762T>C		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+1762T>C		intron	N/A	ENSP00000276410.3
	CHRNA6	ENST00000534622.5	TSL:2	c.219+1762T>C		intron	N/A	ENSP00000433871.1
	CHRNA6	ENST00000533810.5	TSL:4	c.-19+1762T>C		intron	N/A	ENSP00000434659.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54712 AN: 152004 Hom.: 14040 Cov.: 32

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.360 AC: 54818 AN: 152122 Hom.: 14088 Cov.: 32 AF XY: 0.354 AC XY: 26339 AN XY: 74366

African (AFR) AF: 0.731 AC: 30303 AN: 41478

American (AMR) AF: 0.313 AC: 4791 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1106 AN: 5178

South Asian (SAS) AF: 0.207 AC: 997 AN: 4806

European-Finnish (FIN) AF: 0.185 AC: 1964 AN: 10612

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14003 AN: 67978

Other (OTH) AF: 0.336 AC: 708 AN: 2108

Alfa AF: 0.316 Hom.: 1374

Bravo AF: 0.389

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.88
DANN	Benign	0.33
PhyloP100		-0.49
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: rs2217732; hg19: chr8-42618446;