Genetic Variant CHRNA3:c.*163delA (chr15-78596440-AT-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000743.5(CHRNA3):c.*163delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 13673 hom., cov: 0)

Exomes 𝑓: 0.36 ( 42247 hom. )

Consequence

CHRNA3
NM_000743.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.998

Publications

2 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 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.*163delA	3_prime_UTR	Exon 6 of 6	NP_000734.2
CHRNA3	NM_001166694.2		c.1390-3250delA	intron	N/A	NP_001160166.1	P32297-3
CHRNA3	NR_046313.2		n.1784+99delA	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRNA3	ENST00000326828.6	TSL:1 MANE Select	c.*163delA	3_prime_UTR	Exon 6 of 6	ENSP00000315602.5	P32297-2
CHRNA3	ENST00000348639.7	TSL:1	c.1390-3250delA	intron	N/A	ENSP00000267951.4	P32297-3
CHRNA3	ENST00000559002.5	TSL:1	n.193+99delA	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.402

AC:

60229

AN:

149666

Hom.:

13644

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.528

Gnomad ASJ

AF:

0.275

Gnomad EAS

AF:

0.785

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.277

Gnomad OTH

AF:

0.390

GnomAD4 exome

AF:

0.362

AC:

329978

AN:

912316

Hom.:

42247

Cov.:

AF XY:

0.362

AC XY:

157177

AN XY:

434686

show subpopulations

African (AFR)

AF:

0.555

AC:

11670

AN:

21012

American (AMR)

AF:

0.539

AC:

4863

AN:

9022

Ashkenazi Jewish (ASJ)

AF:

0.327

AC:

4037

AN:

12334

East Asian (EAS)

AF:

0.741

AC:

15423

AN:

20812

South Asian (SAS)

AF:

0.439

AC:

12258

AN:

27900

European-Finnish (FIN)

AF:

0.354

AC:

7004

AN:

19758

Middle Eastern (MID)

AF:

0.391

AC:

1003

AN:

2568

European-Non Finnish (NFE)

AF:

0.340

AC:

258818

AN:

760972

Other (OTH)

AF:

0.393

AC:

14902

AN:

37938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

11231

22461

33692

44922

56153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10222

20444

30666

40888

51110

<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:

0.403

AC:

60310

AN:

149772

Hom.:

13673

Cov.:

AF XY:

0.409

AC XY:

29874

AN XY:

73070

show subpopulations

African (AFR)

AF:

0.540

AC:

22147

AN:

40986

American (AMR)

AF:

0.529

AC:

7967

AN:

15066

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

948

AN:

3442

East Asian (EAS)

AF:

0.786

AC:

4033

AN:

5134

South Asian (SAS)

AF:

0.457

AC:

2167

AN:

4746

European-Finnish (FIN)

AF:

0.334

AC:

3320

AN:

9948

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.277

AC:

18640

AN:

67176

Other (OTH)

AF:

0.396

AC:

822

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1645

3290

4935

6580

8225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.162

Hom.:

256

Bravo

AF:

0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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