Variant rs1051730 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000743.5(CHRNA3):c.645C>T(p.Tyr215=) variant causes a synonymous change. The variant allele was found at a frequency of 0.305 in 1,613,104 control chromosomes in the GnomAD database, including 80,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 6058 hom., cov: 31)

Exomes 𝑓: 0.31 ( 74434 hom. )

Consequence

CHRNA3
NM_000743.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:2

Conservation

PhyloP100: 5.50

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 15-78601997-G-A is Benign according to our data. Variant chr15-78601997-G-A is described in ClinVar as [Benign]. Clinvar id is 17503.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CHRNA3	NM_000743.5 linkuse as main transcript	c.645C>T	p.Tyr215=	synonymous_variant	5/6	ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2 linkuse as main transcript	c.645C>T	p.Tyr215=	synonymous_variant	5/6		NP_001160166.1
CHRNA3	XM_006720382.4 linkuse as main transcript	c.444C>T	p.Tyr148=	synonymous_variant	5/6		XP_006720445.1
CHRNA3	NR_046313.2 linkuse as main transcript	n.847C>T		non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6 linkuse as main transcript	c.645C>T	p.Tyr215=	synonymous_variant	5/6	1	NM_000743.5	ENSP00000315602	P1	P32297-2
CHRNA3	ENST00000348639.7 linkuse as main transcript	c.645C>T	p.Tyr215=	synonymous_variant	5/6	1		ENSP00000267951		P32297-3
CHRNA3	ENST00000558903.1 linkuse as main transcript	n.352C>T		non_coding_transcript_exon_variant	2/2	4
CHRNA3	ENST00000559658.5 linkuse as main transcript	c.645C>T	p.Tyr215=	synonymous_variant, NMD_transcript_variant	5/8	2		ENSP00000452896		P32297-2

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39177

AN:

151744

Hom.:

6060

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.0320

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.326

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.295

GnomAD3 exomes

AF:

0.269

AC:

67652

AN:

251254

Hom.:

10777

AF XY:

0.279

AC XY:

37940

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.166

Gnomad ASJ exome

AF:

0.383

Gnomad EAS exome

AF:

0.0322

Gnomad SAS exome

AF:

0.236

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.349

Gnomad OTH exome

AF:

0.299

GnomAD4 exome

AF:

0.310

AC:

453238

AN:

1461244

Hom.:

74434

Cov.:

AF XY:

0.310

AC XY:

225164

AN XY:

726806

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.176

Gnomad4 ASJ exome

AF:

0.382

Gnomad4 EAS exome

AF:

0.0265

Gnomad4 SAS exome

AF:

0.239

Gnomad4 FIN exome

AF:

0.330

Gnomad4 NFE exome

AF:

0.335

Gnomad4 OTH exome

AF:

0.295

GnomAD4 genome

AF:

0.258

AC:

39187

AN:

151860

Hom.:

6058

Cov.:

AF XY:

0.254

AC XY:

18879

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.234

Gnomad4 ASJ

AF:

0.380

Gnomad4 EAS

AF:

0.0323

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.326

Gnomad4 NFE

AF:

0.348

Gnomad4 OTH

AF:

0.292

Alfa

AF:

0.324

Hom.:

15344

Bravo

AF:

0.244

Asia WGS

AF:

0.117

AC:

412

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Lung cancer susceptibility 2

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

May 01, 2008

- -

Smoking as a quantitative trait locus 3

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

May 01, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.6

DANN

Benign

0.56

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