8-42753056-G-C

Variant names:

• chr8-42753056-G-C
• rs2304297
• NM_004198.3:c.*123C>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.*123C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 828,322 control chromosomes in the GnomAD database, including 40,149 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 0.38 (15643 hom., cov: 32)
  • Exomes 𝑓: 0.25 (24506 hom.)
• Consequence: CHRNA6 NM_004198.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510
• Publications: 52 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 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.*123C>G		3_prime_UTR	Exon 6 of 6	NP_004189.1
	CHRNA6	NM_001199279.1		c.*123C>G		3_prime_UTR	Exon 5 of 5	NP_001186208.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA6	ENST00000276410.7	TSL:1 MANE Select	c.*123C>G		3_prime_UTR	Exon 6 of 6	ENSP00000276410.3
	CHRNA6	ENST00000534622.5	TSL:2	c.*123C>G		3_prime_UTR	Exon 5 of 5	ENSP00000433871.1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58312 AN: 151956 Hom.: 15596 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.353

GnomAD4 exome AF: 0.253 AC: 171043 AN: 676248 Hom.: 24506 Cov.: 9 AF XY: 0.254 AC XY: 89803 AN XY: 353598

African (AFR) AF: 0.780 AC: 13083 AN: 16764

American (AMR) AF: 0.264 AC: 5421 AN: 20534

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 4045 AN: 15028

East Asian (EAS) AF: 0.186 AC: 6204 AN: 33396

South Asian (SAS) AF: 0.308 AC: 16215 AN: 52618

European-Finnish (FIN) AF: 0.206 AC: 7874 AN: 38314

Middle Eastern (MID) AF: 0.337 AC: 894 AN: 2656

European-Non Finnish (NFE) AF: 0.233 AC: 108042 AN: 463702

Other (OTH) AF: 0.279 AC: 9265 AN: 33236

GnomAD4 genome AF: 0.384 AC: 58415 AN: 152074 Hom.: 15643 Cov.: 32 AF XY: 0.378 AC XY: 28104 AN XY: 74356

African (AFR) AF: 0.766 AC: 31761 AN: 41456

American (AMR) AF: 0.297 AC: 4537 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 965 AN: 3470

East Asian (EAS) AF: 0.215 AC: 1111 AN: 5176

South Asian (SAS) AF: 0.295 AC: 1421 AN: 4816

European-Finnish (FIN) AF: 0.196 AC: 2077 AN: 10588

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.229 AC: 15590 AN: 67992

Other (OTH) AF: 0.353 AC: 745 AN: 2112

Alfa AF: 0.319 Hom.: 1382

Bravo AF: 0.408

Asia WGS AF: 0.309 AC: 1076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.38
PhyloP100		0.51
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: rs2304297; hg19: chr8-42608199; COSMIC: COSV52381606; COSMIC: COSV52381606;