Genetic Variant CHRNA6:c.219+207G>C (chr8-42764858-C-G) – 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.219+207G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 558,454 control chromosomes in the GnomAD database, including 20,028 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 0.31 ( 10248 hom., cov: 32)

Exomes 𝑓: 0.20 ( 9780 hom. )

Consequence

CHRNA6
NM_004198.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.155

Publications

13 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=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CHRNA6	NM_004198.3 link	c.219+207G>C	intron_variant	Intron 2 of 5	ENST00000276410.7	NP_004189.1	Q15825-1
CHRNA6	NM_001199279.1 link	c.219+207G>C	intron_variant	Intron 2 of 4		NP_001186208.1	Q15825-2
CHRNA6	XM_047422396.1 link	c.219+207G>C	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 link	c.219+207G>C		intron_variant	Intron 2 of 5	1	NM_004198.3	ENSP00000276410.3		Q15825-1

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47360

AN:

151912

Hom.:

10215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.611

Gnomad AMI

AF:

0.0956

Gnomad AMR

AF:

0.294

Gnomad ASJ

AF:

0.211

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.308

GnomAD4 exome

AF:

0.203

AC:

82562

AN:

406424

Hom.:

9780

AF XY:

0.202

AC XY:

42754

AN XY:

212142

show subpopulations

African (AFR)

AF:

0.614

AC:

7085

AN:

11540

American (AMR)

AF:

0.290

AC:

4733

AN:

16336

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

2514

AN:

12232

East Asian (EAS)

AF:

0.179

AC:

5096

AN:

28404

South Asian (SAS)

AF:

0.205

AC:

7500

AN:

36522

European-Finnish (FIN)

AF:

0.164

AC:

4336

AN:

26476

Middle Eastern (MID)

AF:

0.232

AC:

415

AN:

1790

European-Non Finnish (NFE)

AF:

0.182

AC:

45479

AN:

249584

Other (OTH)

AF:

0.230

AC:

5404

AN:

23540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

2929

5859

8788

11718

14647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.312

AC:

47452

AN:

152030

Hom.:

10248

Cov.:

AF XY:

0.306

AC XY:

22773

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.612

AC:

25335

AN:

41418

American (AMR)

AF:

0.293

AC:

4478

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

732

AN:

3468

East Asian (EAS)

AF:

0.215

AC:

1109

AN:

5164

South Asian (SAS)

AF:

0.200

AC:

964

AN:

4814

European-Finnish (FIN)

AF:

0.151

AC:

1600

AN:

10584

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.183

AC:

12432

AN:

68008

Other (OTH)

AF:

0.309

AC:

652

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1372

2745

4117

5490

6862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.255

Hom.:

840

Bravo

AF:

0.340

Asia WGS

AF:

0.266

AC:

924

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.2

(source)

DANN

Benign

0.60

PhyloP100

0.15

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