rs10087172

Variant names:

• chr8-42761725-T-C
• rs10087172
• NM_004198.3:c.220-2612A>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.220-2612A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,174 control chromosomes in the GnomAD database, including 13,991 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 (13991 hom., cov: 33)
• Consequence: CHRNA6 NM_004198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 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.220-2612A>G		intron	N/A	NP_004189.1
	CHRNA6	NM_001199279.1		c.219+3340A>G		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.220-2612A>G		intron	N/A	ENSP00000276410.3
	CHRNA6	ENST00000534622.5	TSL:2	c.219+3340A>G		intron	N/A	ENSP00000433871.1
	CHRNA6	ENST00000533810.5	TSL:4	c.-18-2612A>G		intron	N/A	ENSP00000434659.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54243 AN: 152056 Hom.: 13943 Cov.: 33

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.357 AC: 54351 AN: 152174 Hom.: 13991 Cov.: 33 AF XY: 0.351 AC XY: 26136 AN XY: 74412

African (AFR) AF: 0.730 AC: 30281 AN: 41494

American (AMR) AF: 0.311 AC: 4756 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3468

East Asian (EAS) AF: 0.213 AC: 1101 AN: 5174

South Asian (SAS) AF: 0.205 AC: 990 AN: 4824

European-Finnish (FIN) AF: 0.182 AC: 1933 AN: 10612

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13668 AN: 68000

Other (OTH) AF: 0.335 AC: 709 AN: 2116

Alfa AF: 0.310 Hom.: 2384

Bravo AF: 0.386

Asia WGS AF: 0.272 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.60
PhyloP100		-0.83
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: rs10087172; hg19: chr8-42616868;