dbSNP rs8029939: CHRNA3:c.*597C>T (chr15-78596007-G-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_000743.5(CHRNA3):c.*597C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00833 in 944,248 control chromosomes in the GnomAD database, including 484 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 0.036 ( 331 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 153 hom. )

Consequence

CHRNA3
NM_000743.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.646

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:

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=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5 link	c.*597C>T	3_prime_UTR_variant	Exon 6 of 6	ENST00000326828.6	NP_000734.2	P32297-2
CHRNA3	XM_006720382.4 link	c.*597C>T	3_prime_UTR_variant	Exon 6 of 6		XP_006720445.1
CHRNA3	NM_001166694.2 link	c.1390-2816C>T	intron_variant	Intron 5 of 5		NP_001160166.1	P32297-3
CHRNA3	NR_046313.2 link	n.1784+533C>T	intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHRNA3	ENST00000326828.6 link	c.*597C>T	3_prime_UTR_variant	Exon 6 of 6	1	NM_000743.5	ENSP00000315602.5	P32297-2
CHRNA3	ENST00000348639.7 link	c.1390-2816C>T	intron_variant	Intron 5 of 5	1		ENSP00000267951.4	P32297-3
CHRNA3	ENST00000559002.5 link	n.193+533C>T	intron_variant	Intron 1 of 1	1
CHRNA3	ENST00000559658.5 link	n.*64+533C>T	intron_variant	Intron 6 of 7	2		ENSP00000452896.1	P32297-2

Frequencies

GnomAD3 genomes

AF:

0.0357

AC:

5433

AN:

152118

Hom.:

332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0129

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.0254

GnomAD4 exome

AF:

0.00306

AC:

2427

AN:

792012

Hom.:

153

Cov.:

AF XY:

0.00276

AC XY:

1013

AN XY:

366614

show subpopulations

African (AFR)

AF:

0.136

AC:

2004

AN:

14742

American (AMR)

AF:

0.00426

AC:

AN:

938

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

AN:

4878

East Asian (EAS)

AF:

0.00

AC:

AN:

3342

South Asian (SAS)

AF:

0.000193

AC:

AN:

15510

European-Finnish (FIN)

AF:

0.00

AC:

AN:

260

Middle Eastern (MID)

AF:

0.00461

AC:

AN:

1520

European-Non Finnish (NFE)

AF:

0.000167

AC:

121

AN:

724854

Other (OTH)

AF:

0.00736

AC:

191

AN:

25968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

191

287

382

478

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<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:

0.0357

AC:

5434

AN:

152236

Hom.:

331

Cov.:

AF XY:

0.0350

AC XY:

2605

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.122

AC:

5085

AN:

41516

American (AMR)

AF:

0.0129

AC:

197

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000397

AC:

AN:

68028

Other (OTH)

AF:

0.0251

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

253

506

758

1011

1264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0257

Hom.:

Bravo

AF:

0.0402

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.1

(source)

DANN

Benign

0.53

PhyloP100

0.65

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