Genetic Variant CHRNA6:c.220-122G>T (chr8-42759235-C-A) – 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.220-122G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 732,570 control chromosomes in the GnomAD database, including 30,168 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 0.35 ( 13355 hom., cov: 31)

Exomes 𝑓: 0.22 ( 16813 hom. )

Consequence

CHRNA6
NM_004198.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.17

Publications

26 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
CHRNA6	NM_004198.3 link	c.220-122G>T	intron_variant	Intron 2 of 5	ENST00000276410.7	NP_004189.1
CHRNA6	NM_001199279.1 link	c.220-2198G>T	intron_variant	Intron 2 of 4		NP_001186208.1
CHRNA6	XM_047422396.1 link	c.220-122G>T	intron_variant	Intron 3 of 6		XP_047278352.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CHRNA6	ENST00000276410.7 link	c.220-122G>T	intron_variant	Intron 2 of 5	1	NM_004198.3	ENSP00000276410.3
CHRNA6	ENST00000534622.5 link	c.220-2198G>T	intron_variant	Intron 2 of 4	2		ENSP00000433871.1
CHRNA6	ENST00000533810.5 link	c.-18-122G>T	intron_variant	Intron 2 of 4	4		ENSP00000434659.1
CHRNA6	ENST00000530869.1 link	n.466-122G>T	intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53257

AN:

151908

Hom.:

13314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.710

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.333

GnomAD4 exome

AF:

0.222

AC:

128944

AN:

580544

Hom.:

16813

Cov.:

AF XY:

0.218

AC XY:

68043

AN XY:

311684

show subpopulations

African (AFR)

AF:

0.713

AC:

11167

AN:

15666

American (AMR)

AF:

0.310

AC:

10414

AN:

33544

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

3652

AN:

17464

East Asian (EAS)

AF:

0.184

AC:

6264

AN:

34094

South Asian (SAS)

AF:

0.204

AC:

12120

AN:

59360

European-Finnish (FIN)

AF:

0.190

AC:

8739

AN:

45902

Middle Eastern (MID)

AF:

0.257

AC:

998

AN:

3890

European-Non Finnish (NFE)

AF:

0.200

AC:

68091

AN:

340160

Other (OTH)

AF:

0.246

AC:

7499

AN:

30464

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

4461

8922

13383

17844

22305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

848

1696

2544

3392

4240

<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:

0.351

AC:

53356

AN:

152026

Hom.:

13355

Cov.:

AF XY:

0.345

AC XY:

25627

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.710

AC:

29438

AN:

41458

American (AMR)

AF:

0.308

AC:

4701

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

739

AN:

3468

East Asian (EAS)

AF:

0.214

AC:

1102

AN:

5158

South Asian (SAS)

AF:

0.198

AC:

950

AN:

4804

European-Finnish (FIN)

AF:

0.182

AC:

1923

AN:

10576

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.201

AC:

13641

AN:

67994

Other (OTH)

AF:

0.333

AC:

704

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1361

2722

4084

5445

6806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<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:

0.241

Hom.:

3672

Bravo

AF:

0.380

Asia WGS

AF:

0.267

AC:

930

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.42

(source)

DANN

Benign

0.55

PhyloP100

-3.2

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