rs2196129

Variant names:

• chr8-42763263-G-C
• rs2196129
• NM_004198.3:c.219+1802C>G

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+1802C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,172 control chromosomes in the GnomAD database, including 1,925 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 (1925 hom., cov: 32)
• Consequence: CHRNA6 NM_004198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.986
• Publications: 4 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 = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA6	NM_004198.3	c.219+1802C>G		intron_variant	Intron 2 of 5	ENST00000276410.7	NP_004189.1
CHRNA6	NM_001199279.1	c.219+1802C>G		intron_variant	Intron 2 of 4		NP_001186208.1
CHRNA6	XM_047422396.1	c.219+1802C>G		intron_variant	Intron 3 of 6		XP_047278352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA6	ENST00000276410.7	c.219+1802C>G		intron_variant	Intron 2 of 5	1	NM_004198.3	ENSP00000276410.3
CHRNA6	ENST00000534622.5	c.219+1802C>G		intron_variant	Intron 2 of 4	2		ENSP00000433871.1
CHRNA6	ENST00000533810.5	c.-19+1802C>G		intron_variant	Intron 2 of 4	4		ENSP00000434659.1
CHRNA6	ENST00000530869.1	n.421+1802C>G		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21700 AN: 152054 Hom.: 1922 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0383

Gnomad FIN AF: 0.0568

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.143 AC: 21738 AN: 152172 Hom.: 1925 Cov.: 32 AF XY: 0.134 AC XY: 10000 AN XY: 74404

African (AFR) AF: 0.235 AC: 9741 AN: 41482

American (AMR) AF: 0.116 AC: 1770 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5190

South Asian (SAS) AF: 0.0379 AC: 183 AN: 4826

European-Finnish (FIN) AF: 0.0568 AC: 602 AN: 10600

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8642 AN: 68010

Other (OTH) AF: 0.142 AC: 301 AN: 2114

Alfa AF: 0.133 Hom.: 190

Bravo AF: 0.153

Asia WGS AF: 0.0380 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.38
PhyloP100		0.99
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2196129; hg19: chr8-42618406;