dbSNP rs8192479: CHRNA3:p.Lys115Lys (chr15-78617056-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_000743.5(CHRNA3):c.345G>A(p.Lys115Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,613,480 control chromosomes in the GnomAD database, including 274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 19 hom., cov: 32)

Exomes 𝑓: 0.017 ( 255 hom. )

Consequence

CHRNA3
NM_000743.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.957

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BP6

Variant 15-78617056-C-T is Benign according to our data. Variant chr15-78617056-C-T is described in ClinVar as [Benign]. Clinvar id is 2123513.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.957 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.013 (1974/152340) while in subpopulation NFE AF= 0.0209 (1420/68040). AF 95% confidence interval is 0.02. There are 19 homozygotes in gnomad4. There are 897 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5 link	c.345G>A	p.Lys115Lys	synonymous_variant	Exon 4 of 6	ENST00000326828.6	NP_000734.2	P32297-2
CHRNA3	NM_001166694.2 link	c.345G>A	p.Lys115Lys	synonymous_variant	Exon 4 of 6		NP_001160166.1	P32297-3
CHRNA3	XM_006720382.4 link	c.144G>A	p.Lys48Lys	synonymous_variant	Exon 4 of 6		XP_006720445.1
CHRNA3	NR_046313.2 link	n.547G>A		non_coding_transcript_exon_variant	Exon 4 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHRNA3	ENST00000326828.6 link	c.345G>A	p.Lys115Lys	synonymous_variant	Exon 4 of 6	1	NM_000743.5	ENSP00000315602.5	P32297-2
CHRNA3	ENST00000348639.7 link	c.345G>A	p.Lys115Lys	synonymous_variant	Exon 4 of 6	1		ENSP00000267951.4	P32297-3
CHRNA3	ENST00000559658.5 link	n.345G>A		non_coding_transcript_exon_variant	Exon 4 of 8	2		ENSP00000452896.1	P32297-2

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1974

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00321

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00694

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.0241

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0209

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.0129

AC:

3225

AN:

250890

Hom.:

AF XY:

0.0130

AC XY:

1758

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.00327

Gnomad AMR exome

AF:

0.00310

Gnomad ASJ exome

AF:

0.00905

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.0281

Gnomad NFE exome

AF:

0.0199

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.0173

AC:

25349

AN:

1461140

Hom.:

255

Cov.:

AF XY:

0.0170

AC XY:

12355

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.00281

Gnomad4 AMR exome

AF:

0.00396

Gnomad4 ASJ exome

AF:

0.00995

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00160

Gnomad4 FIN exome

AF:

0.0276

Gnomad4 NFE exome

AF:

0.0200

Gnomad4 OTH exome

AF:

0.0164

GnomAD4 genome

AF:

0.0130

AC:

1974

AN:

152340

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

897

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00320

Gnomad4 AMR

AF:

0.00693

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00165

Gnomad4 FIN

AF:

0.0241

Gnomad4 NFE

AF:

0.0209

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.0161

Hom.:

Bravo

AF:

0.0114

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0185

EpiControl

AF:

0.0193

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.22

CADD

Benign

DANN

Benign

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over