Variant rs1362650 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_021629.4(GNB4):c.117T>C(p.Ser39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,601,116 control chromosomes in the GnomAD database, including 177,775 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 16872 hom., cov: 32)

Exomes 𝑓: 0.47 ( 160903 hom. )

Consequence

GNB4
NM_021629.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.67

Variant links:

Genes affected

GNB4 (HGNC:20731): (G protein subunit beta 4) 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. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. [provided by RefSeq, Jul 2008]

GNB4 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=-0.87).

BP6

Variant 3-179419485-A-G is Benign according to our data. Variant chr3-179419485-A-G is described in ClinVar as [Benign]. Clinvar id is 261427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-179419485-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNB4	NM_021629.4 linkuse as main transcript	c.117T>C	p.Ser39=	synonymous_variant	4/10	ENST00000232564.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNB4	ENST00000232564.8 linkuse as main transcript	c.117T>C	p.Ser39=	synonymous_variant	4/10	1	NM_021629.4	P1

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71358

AN:

151818

Hom.:

16851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.452

Gnomad AMI

AF:

0.463

Gnomad AMR

AF:

0.516

Gnomad ASJ

AF:

0.476

Gnomad EAS

AF:

0.436

Gnomad SAS

AF:

0.511

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.464

Gnomad OTH

AF:

0.471

GnomAD3 exomes

AF:

0.476

AC:

119489

AN:

251164

Hom.:

28618

AF XY:

0.478

AC XY:

64893

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.448

Gnomad AMR exome

AF:

0.503

Gnomad ASJ exome

AF:

0.475

Gnomad EAS exome

AF:

0.429

Gnomad SAS exome

AF:

0.514

Gnomad FIN exome

AF:

0.500

Gnomad NFE exome

AF:

0.464

Gnomad OTH exome

AF:

0.473

GnomAD4 exome

AF:

0.469

AC:

679732

AN:

1449180

Hom.:

160903

Cov.:

AF XY:

0.472

AC XY:

340343

AN XY:

721738

show subpopulations

Gnomad4 AFR exome

AF:

0.445

Gnomad4 AMR exome

AF:

0.504

Gnomad4 ASJ exome

AF:

0.482

Gnomad4 EAS exome

AF:

0.464

Gnomad4 SAS exome

AF:

0.515

Gnomad4 FIN exome

AF:

0.505

Gnomad4 NFE exome

AF:

0.463

Gnomad4 OTH exome

AF:

0.469

GnomAD4 genome

AF:

0.470

AC:

71404

AN:

151936

Hom.:

16872

Cov.:

AF XY:

0.471

AC XY:

34976

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.451

Gnomad4 AMR

AF:

0.516

Gnomad4 ASJ

AF:

0.476

Gnomad4 EAS

AF:

0.436

Gnomad4 SAS

AF:

0.509

Gnomad4 FIN

AF:

0.512

Gnomad4 NFE

AF:

0.464

Gnomad4 OTH

AF:

0.476

Alfa

AF:

0.467

Hom.:

21437

Bravo

AF:

0.466

Asia WGS

AF:

0.491

AC:

1703

AN:

3478

EpiCase

AF:

0.469

EpiControl

AF:

0.476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease dominant intermediate F

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

Cadd

Benign

2.4

Dann

Benign

0.55

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