Variant 15-78618839-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000743.5(CHRNA3):c.159A>G(p.Val53=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,613,816 control chromosomes in the GnomAD database, including 117,850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10647 hom., cov: 33)

Exomes 𝑓: 0.38 ( 107203 hom. )

Consequence

CHRNA3
NM_000743.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.197

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 15-78618839-T-C is Benign according to our data. Variant chr15-78618839-T-C is described in ClinVar as [Benign]. Clinvar id is 1209688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.197 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CHRNA3	NM_000743.5 linkuse as main transcript	c.159A>G	p.Val53=	synonymous_variant	2/6	ENST00000326828.6
CHRNA3	NM_001166694.2 linkuse as main transcript	c.159A>G	p.Val53=	synonymous_variant	2/6
CHRNA3	XM_006720382.4 linkuse as main transcript	c.-43A>G		5_prime_UTR_variant	2/6
CHRNA3	NR_046313.2 linkuse as main transcript	n.361A>G		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA3	ENST00000326828.6 linkuse as main transcript	c.159A>G	p.Val53=	synonymous_variant	2/6	1	NM_000743.5	P1	P32297-2

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56346

AN:

152044

Hom.:

10641

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.442

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.259

Gnomad FIN

AF:

0.374

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.405

Gnomad OTH

AF:

0.393

GnomAD3 exomes

AF:

0.353

AC:

88657

AN:

251302

Hom.:

16512

AF XY:

0.357

AC XY:

48490

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.340

Gnomad AMR exome

AF:

0.224

Gnomad ASJ exome

AF:

0.427

Gnomad EAS exome

AF:

0.364

Gnomad SAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.372

Gnomad NFE exome

AF:

0.404

Gnomad OTH exome

AF:

0.363

GnomAD4 exome

AF:

0.380

AC:

555700

AN:

1461654

Hom.:

107203

Cov.:

AF XY:

0.378

AC XY:

274522

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.343

Gnomad4 AMR exome

AF:

0.237

Gnomad4 ASJ exome

AF:

0.425

Gnomad4 EAS exome

AF:

0.355

Gnomad4 SAS exome

AF:

0.271

Gnomad4 FIN exome

AF:

0.379

Gnomad4 NFE exome

AF:

0.395

Gnomad4 OTH exome

AF:

0.374

GnomAD4 genome

AF:

0.371

AC:

56389

AN:

152162

Hom.:

10647

Cov.:

AF XY:

0.367

AC XY:

27285

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.340

Gnomad4 AMR

AF:

0.321

Gnomad4 ASJ

AF:

0.424

Gnomad4 EAS

AF:

0.347

Gnomad4 SAS

AF:

0.261

Gnomad4 FIN

AF:

0.374

Gnomad4 NFE

AF:

0.405

Gnomad4 OTH

AF:

0.389

Alfa

AF:

0.390

Hom.:

17625

Bravo

AF:

0.365

Asia WGS

AF:

0.260

AC:

909

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Urinary bladder, atony of

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.65

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