dbSNP rs4243084: CHRNA3:c.83-415C>G (chr15-78619330-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_000743.5(CHRNA3):c.83-415C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 197,522 control chromosomes in the GnomAD database, including 9,334 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 0.30 ( 7162 hom., cov: 33)

Exomes 𝑓: 0.29 ( 2172 hom. )

Consequence

CHRNA3
NM_000743.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.414

Publications

23 publications found

Variant links:

Genes affected

CHRNA3 (HGNC:1957): (cholinergic receptor nicotinic alpha 3 subunit) This locus encodes a member of the nicotinic acetylcholine receptor family of proteins. Members of this family of proteins form pentameric complexes comprised of both alpha and beta subunits. This locus encodes an alpha-type subunit, as it contains characteristic adjacent cysteine residues. The encoded protein is a ligand-gated ion channel that likely plays a role in neurotransmission. Polymorphisms in this gene have been associated with an increased risk of smoking initiation and an increased susceptibility to lung cancer. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

CHRNA3 Gene-Disease associations (from GenCC):

urinary bladder, atony of
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, G2P

CHRNA3 links:

Genome browser will be placed here

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=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5 link	c.83-415C>G	intron_variant	Intron 1 of 5	ENST00000326828.6	NP_000734.2	P32297-2
CHRNA3	NM_001166694.2 link	c.83-415C>G	intron_variant	Intron 1 of 5		NP_001160166.1	P32297-3
CHRNA3	NR_046313.2 link	n.285-415C>G	intron_variant	Intron 1 of 7
CHRNA3	XM_006720382.4 link	c.-120+407C>G	intron_variant	Intron 1 of 5		XP_006720445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6 link	c.83-415C>G		intron_variant	Intron 1 of 5	1	NM_000743.5	ENSP00000315602.5		P32297-2

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45093

AN:

152078

Hom.:

7161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.383

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.327

GnomAD4 exome

AF:

0.294

AC:

13312

AN:

45326

Hom.:

2172

AF XY:

0.288

AC XY:

6779

AN XY:

23504

show subpopulations

African (AFR)

AF:

0.151

AC:

221

AN:

1464

American (AMR)

AF:

0.251

AC:

908

AN:

3616

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

388

AN:

1082

East Asian (EAS)

AF:

0.257

AC:

705

AN:

2746

South Asian (SAS)

AF:

0.228

AC:

1139

AN:

4994

European-Finnish (FIN)

AF:

0.324

AC:

436

AN:

1346

Middle Eastern (MID)

AF:

0.365

AC:

AN:

156

European-Non Finnish (NFE)

AF:

0.317

AC:

8723

AN:

27516

Other (OTH)

AF:

0.305

AC:

735

AN:

2406

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

452

904

1357

1809

2261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<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:

0.296

AC:

45121

AN:

152196

Hom.:

7162

Cov.:

AF XY:

0.294

AC XY:

21902

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.191

AC:

7942

AN:

41528

American (AMR)

AF:

0.282

AC:

4318

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

1326

AN:

3464

East Asian (EAS)

AF:

0.278

AC:

1442

AN:

5178

South Asian (SAS)

AF:

0.238

AC:

1150

AN:

4830

European-Finnish (FIN)

AF:

0.347

AC:

3673

AN:

10584

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.354

AC:

24068

AN:

67990

Other (OTH)

AF:

0.325

AC:

686

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1631

3262

4894

6525

8156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

446

892

1338

1784

2230

<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:

0.312

Hom.:

965

Bravo

AF:

0.286

Asia WGS

AF:

0.217

AC:

757

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.84

(source)

DANN

Benign

0.41

PhyloP100

-0.41

PromoterAI

-0.023

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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