Genetic Variant CHRNA3:c.83-90G>A (chr15-78619005-C-T) – 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.83-90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,423,450 control chromosomes in the GnomAD database, including 116 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 0.016 ( 55 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 61 hom. )

Consequence

CHRNA3
NM_000743.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.130

Publications

3 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:

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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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5 link	c.83-90G>A	intron_variant	Intron 1 of 5	ENST00000326828.6	NP_000734.2	P32297-2
CHRNA3	NM_001166694.2 link	c.83-90G>A	intron_variant	Intron 1 of 5		NP_001160166.1	P32297-3
CHRNA3	NR_046313.2 link	n.285-90G>A	intron_variant	Intron 1 of 7
CHRNA3	XM_006720382.4 link	c.-119-90G>A	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.83-90G>A		intron_variant	Intron 1 of 5	1	NM_000743.5	ENSP00000315602.5		P32297-2

Frequencies

GnomAD3 genomes

AF:

0.0160

AC:

2442

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0541

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.0110

GnomAD4 exome

AF:

0.00220

AC:

2796

AN:

1271128

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

1270

AN XY:

635696

show subpopulations

African (AFR)

AF:

0.0569

AC:

1683

AN:

29600

American (AMR)

AF:

0.00346

AC:

138

AN:

39898

Ashkenazi Jewish (ASJ)

AF:

0.0204

AC:

448

AN:

21926

East Asian (EAS)

AF:

0.0000516

AC:

AN:

38790

South Asian (SAS)

AF:

0.000213

AC:

AN:

75190

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40424

Middle Eastern (MID)

AF:

0.00598

AC:

AN:

3676

European-Non Finnish (NFE)

AF:

0.000219

AC:

212

AN:

967824

Other (OTH)

AF:

0.00509

AC:

274

AN:

53800

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

142

285

427

570

712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<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:

0.0161

AC:

2452

AN:

152322

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

1148

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0542

AC:

2254

AN:

41560

American (AMR)

AF:

0.00496

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000573

AC:

AN:

68026

Other (OTH)

AF:

0.0109

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

110

221

331

442

552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00814

Hom.:

Bravo

AF:

0.0180

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.9

(source)

DANN

Benign

0.44

PhyloP100

0.13

PromoterAI

0.0069

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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