Variant rs4952 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000749.5(CHRNB3):c.615C>T(p.Asn205=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 1,614,024 control chromosomes in the GnomAD database, including 1,728 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 0.032 ( 122 hom., cov: 33)

Exomes 𝑓: 0.041 ( 1606 hom. )

Consequence

CHRNB3
NM_000749.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0230

Variant links:

Genes affected

CHRNB3 (HGNC:1963): (cholinergic receptor nicotinic beta 3 subunit) The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The nAChRs are (hetero)pentamers composed of homologous subunits. The subunits that make up the muscle and neuronal forms of nAChRs are encoded by separate genes and have different primary structure. There are several subtypes of neuronal nAChRs that vary based on which homologous subunits are arranged around the central channel. They are classified as alpha-subunits if, like muscle alpha-1 (MIM 100690), they have a pair of adjacent cysteines as part of the presumed acetylcholine binding site. Subunits lacking these cysteine residues are classified as beta-subunits (Groot Kormelink and Luyten, 1997 [PubMed 9009220]). Elliott et al. (1996) [PubMed 8906617] stated that the proposed structure for each subunit is a conserved N-terminal extracellular domain followed by 3 conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region.[supplied by OMIM, Apr 2010]

CHRNB3 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=-0.77).

BP7

Synonymous conserved (PhyloP=-0.023 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CHRNB3	NM_000749.5 linkuse as main transcript	c.615C>T	p.Asn205=	synonymous_variant	5/6	ENST00000289957.3	NP_000740.1
CHRNB3	NM_001347717.2 linkuse as main transcript	c.393C>T	p.Asn131=	synonymous_variant	6/7		NP_001334646.1
CHRNB3	XM_011544390.3 linkuse as main transcript	c.228C>T	p.Asn76=	synonymous_variant	3/4		XP_011542692.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB3	ENST00000289957.3 linkuse as main transcript	c.615C>T	p.Asn205=	synonymous_variant	5/6	1	NM_000749.5	ENSP00000289957	P1

Frequencies

GnomAD3 genomes

AF:

0.0321

AC:

4888

AN:

152040

Hom.:

122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00921

Gnomad AMI

AF:

0.0738

Gnomad AMR

AF:

0.0293

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0786

Gnomad FIN

AF:

0.0499

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0382

Gnomad OTH

AF:

0.0368

GnomAD3 exomes

AF:

0.0435

AC:

10931

AN:

251458

Hom.:

390

AF XY:

0.0478

AC XY:

6491

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00954

Gnomad AMR exome

AF:

0.0247

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.000652

Gnomad SAS exome

AF:

0.0857

Gnomad FIN exome

AF:

0.0480

Gnomad NFE exome

AF:

0.0430

Gnomad OTH exome

AF:

0.0544

GnomAD4 exome

AF:

0.0405

AC:

59242

AN:

1461866

Hom.:

1606

Cov.:

AF XY:

0.0430

AC XY:

31279

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0113

Gnomad4 AMR exome

AF:

0.0246

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.0878

Gnomad4 FIN exome

AF:

0.0466

Gnomad4 NFE exome

AF:

0.0374

Gnomad4 OTH exome

AF:

0.0468

GnomAD4 genome

AF:

0.0321

AC:

4877

AN:

152158

Hom.:

122

Cov.:

AF XY:

0.0323

AC XY:

2405

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00918

Gnomad4 AMR

AF:

0.0293

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0785

Gnomad4 FIN

AF:

0.0499

Gnomad4 NFE

AF:

0.0382

Gnomad4 OTH

AF:

0.0360

Alfa

AF:

0.0416

Hom.:

210

Bravo

AF:

0.0294

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

EpiCase

AF:

0.0483

EpiControl

AF:

0.0478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.20

DANN

Benign

0.66

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over