rs5443

Positions:

chr12-6845711-C-T

Variant summary

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

The NM_002075.4(GNB3):c.825C>T(p.Ser275=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,613,364 control chromosomes in the GnomAD database, including 100,362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 17424 hom., cov: 32)

Exomes 𝑓: 0.33 ( 82938 hom. )

Consequence

GNB3
NM_002075.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -4.90

Variant links:

Genes affected

GNB3 (HGNC:4400): (G protein subunit beta 3) Heterotrimeric guanine nucleotide-binding proteins (G proteins), which integrate signals between receptors and effector proteins, are composed of an alpha, a beta, and a gamma subunit. These subunits are encoded by families of related genes. This gene encodes a beta subunit which belongs to the WD repeat G protein beta family. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. A single-nucleotide polymorphism (C825T) in this gene is associated with essential hypertension and obesity. This polymorphism is also associated with the occurrence of the splice variant GNB3-s, which appears to have increased activity. GNB3-s is an example of alternative splicing caused by a nucleotide change outside of the splice donor and acceptor sites. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Jul 2014]

GNB3 links:

CDCA3 (HGNC:14624): (cell division cycle associated 3) Predicted to be involved in cell division and protein ubiquitination. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

CDCA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 12-6845711-C-T is Benign according to our data. Variant chr12-6845711-C-T is described in ClinVar as [Benign]. Clinvar id is 226004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.9 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNB3	NM_002075.4 linkuse as main transcript	c.825C>T	p.Ser275=	synonymous_variant	9/10	ENST00000229264.8	NP_002066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNB3	ENST00000229264.8 linkuse as main transcript	c.825C>T	p.Ser275=	synonymous_variant	9/10	5	NM_002075.4	ENSP00000229264	P1	P16520-1

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66665

AN:

151972

Hom.:

17391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.738

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.508

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.248

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.446

GnomAD3 exomes

AF:

0.357

AC:

89686

AN:

251406

Hom.:

18076

AF XY:

0.347

AC XY:

47203

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.756

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.319

Gnomad EAS exome

AF:

0.524

Gnomad SAS exome

AF:

0.320

Gnomad FIN exome

AF:

0.255

Gnomad NFE exome

AF:

0.308

Gnomad OTH exome

AF:

0.336

GnomAD4 exome

AF:

0.326

AC:

476344

AN:

1461274

Hom.:

82938

Cov.:

AF XY:

0.325

AC XY:

236257

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.764

Gnomad4 AMR exome

AF:

0.356

Gnomad4 ASJ exome

AF:

0.321

Gnomad4 EAS exome

AF:

0.513

Gnomad4 SAS exome

AF:

0.321

Gnomad4 FIN exome

AF:

0.257

Gnomad4 NFE exome

AF:

0.306

Gnomad4 OTH exome

AF:

0.359

GnomAD4 genome

AF:

0.439

AC:

66758

AN:

152090

Hom.:

17424

Cov.:

AF XY:

0.434

AC XY:

32272

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.738

Gnomad4 AMR

AF:

0.402

Gnomad4 ASJ

AF:

0.316

Gnomad4 EAS

AF:

0.508

Gnomad4 SAS

AF:

0.316

Gnomad4 FIN

AF:

0.248

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.450

Alfa

AF:

0.338

Hom.:

16366

Bravo

AF:

0.466

Asia WGS

AF:

0.421

AC:

1461

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Congenital stationary night blindness 1H

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

GNB3 POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Apr 01, 2003

- -

GNB3-related condition

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 24, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hypertension, essential, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Apr 01, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.22

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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