15-78617110-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000743.5(CHRNA3):c.291A>G(p.Lys97Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 1,610,160 control chromosomes in the GnomAD database, including 323,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30013 hom., cov: 32)

Exomes 𝑓: 0.63 ( 293831 hom. )

Consequence

CHRNA3
NM_000743.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.731

Publications

54 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 15-78617110-T-C is Benign according to our data. Variant chr15-78617110-T-C is described in ClinVar as Benign. ClinVar VariationId is 1209767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.731 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CHRNA3	NM_000743.5 link	c.291A>G	p.Lys97Lys	synonymous_variant	Exon 4 of 6	ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2 link	c.291A>G	p.Lys97Lys	synonymous_variant	Exon 4 of 6		NP_001160166.1
CHRNA3	XM_006720382.4 link	c.90A>G	p.Lys30Lys	synonymous_variant	Exon 4 of 6		XP_006720445.1
CHRNA3	NR_046313.2 link	n.493A>G		non_coding_transcript_exon_variant	Exon 4 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CHRNA3	ENST00000326828.6 link	c.291A>G	p.Lys97Lys	synonymous_variant	Exon 4 of 6	1	NM_000743.5	ENSP00000315602.5
CHRNA3	ENST00000348639.7 link	c.291A>G	p.Lys97Lys	synonymous_variant	Exon 4 of 6	1		ENSP00000267951.4
CHRNA3	ENST00000559658.5 link	n.291A>G		non_coding_transcript_exon_variant	Exon 4 of 8	2		ENSP00000452896.1

Frequencies

GnomAD3 genomes

AF:

0.625

AC:

94868

AN:

151894

Hom.:

29976

Cov.:

show subpopulations

Gnomad AFR

AF:

0.561

Gnomad AMI

AF:

0.594

Gnomad AMR

AF:

0.752

Gnomad ASJ

AF:

0.638

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.675

Gnomad FIN

AF:

0.650

Gnomad MID

AF:

0.793

Gnomad NFE

AF:

0.630

Gnomad OTH

AF:

0.654

GnomAD2 exomes

AF:

0.662

AC:

165601

AN:

250308

AF XY:

0.661

show subpopulations

Gnomad AFR exome

AF:

0.566

Gnomad AMR exome

AF:

0.838

Gnomad ASJ exome

AF:

0.656

Gnomad EAS exome

AF:

0.562

Gnomad FIN exome

AF:

0.659

Gnomad NFE exome

AF:

0.629

Gnomad OTH exome

AF:

0.661

GnomAD4 exome

AF:

0.632

AC:

922035

AN:

1458148

Hom.:

293831

Cov.:

AF XY:

0.633

AC XY:

459598

AN XY:

725526

show subpopulations

African (AFR)

AF:

0.569

AC:

19007

AN:

33422

American (AMR)

AF:

0.828

AC:

37002

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.642

AC:

16773

AN:

26110

East Asian (EAS)

AF:

0.577

AC:

22890

AN:

39684

South Asian (SAS)

AF:

0.687

AC:

59163

AN:

86130

European-Finnish (FIN)

AF:

0.655

AC:

34833

AN:

53204

Middle Eastern (MID)

AF:

0.726

AC:

4183

AN:

5760

European-Non Finnish (NFE)

AF:

0.622

AC:

690117

AN:

1108912

Other (OTH)

AF:

0.632

AC:

38067

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

15488

30975

46463

61950

77438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18462

36924

55386

73848

92310

<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:

0.625

AC:

94953

AN:

152012

Hom.:

30013

Cov.:

AF XY:

0.626

AC XY:

46528

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.561

AC:

23259

AN:

41448

American (AMR)

AF:

0.753

AC:

11510

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.638

AC:

2213

AN:

3470

East Asian (EAS)

AF:

0.561

AC:

2891

AN:

5150

South Asian (SAS)

AF:

0.676

AC:

3263

AN:

4824

European-Finnish (FIN)

AF:

0.650

AC:

6854

AN:

10550

Middle Eastern (MID)

AF:

0.781

AC:

228

AN:

292

European-Non Finnish (NFE)

AF:

0.630

AC:

42802

AN:

67964

Other (OTH)

AF:

0.659

AC:

1391

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1835

3669

5504

7338

9173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

772

1544

2316

3088

3860

<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:

0.620

Hom.:

58024

Bravo

AF:

0.628

Asia WGS

AF:

0.642

AC:

2233

AN:

3478

EpiCase

AF:

0.648

EpiControl

AF:

0.642

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Urinary bladder, atony of

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.3

(source)

DANN

Benign

0.67

PhyloP100

0.73

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over