dbSNP rs2304297: CHRNA6:c.*123C>G (chr8-42753056-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.510

Publications

52 publications found

Variant links:

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]

CHRNA6 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
CHRNA6	NM_004198.3 link	c.*123C>G	3_prime_UTR_variant	Exon 6 of 6	ENST00000276410.7	NP_004189.1
CHRNA6	NM_001199279.1 link	c.*123C>G	3_prime_UTR_variant	Exon 5 of 5		NP_001186208.1
CHRNA6	XM_047422396.1 link	c.*123C>G	3_prime_UTR_variant	Exon 7 of 7		XP_047278352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA6	ENST00000276410.7 link	c.*123C>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_004198.3	ENSP00000276410.3
CHRNA6	ENST00000534622.5 link	c.*123C>G		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000433871.1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58312

AN:

151956

Hom.:

15596

Cov.:

show subpopulations

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.:

AF XY:

0.254

AC XY:

89803

AN XY:

353598

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

5876

11752

17627

23503

29379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2416

4832

7248

9664

12080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.384

AC:

58415

AN:

152074

Hom.:

15643

Cov.:

AF XY:

0.378

AC XY:

28104

AN XY:

74356

show subpopulations

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.229

AC:

15590

AN:

67992

Other (OTH)

AF:

0.353

AC:

745

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1404

2808

4213

5617

7021

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.5

(source)

DANN

Benign

0.38

PhyloP100

0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over