dbSNP rs472054: CHRNA3:c.*952T>C (chr15-78595652-A-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_000743.5(CHRNA3):c.*952T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,708 control chromosomes in the GnomAD database, including 35,427 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 0.68 ( 35287 hom., cov: 31)

Exomes 𝑓: 0.61 ( 140 hom. )

Consequence

CHRNA3
NM_000743.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.29

Publications

25 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=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000743.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRNA3	NM_000743.5	MANE Select	c.*952T>C	3_prime_UTR	Exon 6 of 6	NP_000734.2
CHRNA3	NM_001166694.2		c.1390-2461T>C	intron	N/A	NP_001160166.1	P32297-3
CHRNA3	NR_046313.2		n.1784+888T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRNA3	ENST00000326828.6	TSL:1 MANE Select	c.*952T>C	3_prime_UTR	Exon 6 of 6	ENSP00000315602.5	P32297-2
CHRNA3	ENST00000348639.7	TSL:1	c.1390-2461T>C	intron	N/A	ENSP00000267951.4	P32297-3
CHRNA3	ENST00000559002.5	TSL:1	n.193+888T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.678

AC:

103033

AN:

151864

Hom.:

35243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.716

Gnomad AMI

AF:

0.577

Gnomad AMR

AF:

0.768

Gnomad ASJ

AF:

0.654

Gnomad EAS

AF:

0.818

Gnomad SAS

AF:

0.700

Gnomad FIN

AF:

0.650

Gnomad MID

AF:

0.804

Gnomad NFE

AF:

0.629

Gnomad OTH

AF:

0.694

GnomAD4 exome

AF:

0.609

AC:

442

AN:

726

Hom.:

140

Cov.:

AF XY:

0.630

AC XY:

237

AN XY:

376

show subpopulations

African (AFR)

AF:

0.900

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.833

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.667

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.601

AC:

404

AN:

672

Other (OTH)

AF:

0.607

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.679

AC:

103137

AN:

151982

Hom.:

35287

Cov.:

AF XY:

0.682

AC XY:

50617

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.716

AC:

29663

AN:

41436

American (AMR)

AF:

0.768

AC:

11733

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.654

AC:

2269

AN:

3470

East Asian (EAS)

AF:

0.818

AC:

4243

AN:

5184

South Asian (SAS)

AF:

0.701

AC:

3374

AN:

4810

European-Finnish (FIN)

AF:

0.650

AC:

6853

AN:

10550

Middle Eastern (MID)

AF:

0.793

AC:

233

AN:

294

European-Non Finnish (NFE)

AF:

0.630

AC:

42773

AN:

67944

Other (OTH)

AF:

0.698

AC:

1470

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1676

3353

5029

6706

8382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<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:

0.648

Hom.:

83797

Bravo

AF:

0.689

Asia WGS

AF:

0.755

AC:

2625

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.066

(source)

DANN

Benign

0.56

PhyloP100

-2.3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over