Variant 12-6841239-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002075.4(GNB3):c.-30-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 1,512,448 control chromosomes in the GnomAD database, including 4,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 320 hom., cov: 32)

Exomes 𝑓: 0.070 ( 3725 hom. )

Consequence

GNB3
NM_002075.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.449

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-6841239-G-A is Benign according to our data. Variant chr12-6841239-G-A is described in ClinVar as [Benign]. Clinvar id is 1257613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.073 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.-30-19G>A		intron_variant		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.-30-19G>A		intron_variant		5	NM_002075.4	ENSP00000229264	P1	P16520-1

Frequencies

GnomAD3 genomes

AF:

0.0530

AC:

8034

AN:

151660

Hom.:

320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0492

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.000391

Gnomad SAS

AF:

0.0164

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0747

Gnomad OTH

AF:

0.0436

GnomAD3 exomes

AF:

0.0542

AC:

12085

AN:

222928

Hom.:

470

AF XY:

0.0550

AC XY:

6605

AN XY:

120192

show subpopulations

Gnomad AFR exome

AF:

0.0129

Gnomad AMR exome

AF:

0.0255

Gnomad ASJ exome

AF:

0.0330

Gnomad EAS exome

AF:

0.0000595

Gnomad SAS exome

AF:

0.0192

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.0755

Gnomad OTH exome

AF:

0.0544

GnomAD4 exome

AF:

0.0701

AC:

95389

AN:

1360668

Hom.:

3725

Cov.:

AF XY:

0.0686

AC XY:

46591

AN XY:

679468

show subpopulations

Gnomad4 AFR exome

AF:

0.0101

Gnomad4 AMR exome

AF:

0.0285

Gnomad4 ASJ exome

AF:

0.0356

Gnomad4 EAS exome

AF:

0.0000273

Gnomad4 SAS exome

AF:

0.0200

Gnomad4 FIN exome

AF:

0.130

Gnomad4 NFE exome

AF:

0.0789

Gnomad4 OTH exome

AF:

0.0575

GnomAD4 genome

AF:

0.0529

AC:

8032

AN:

151780

Hom.:

320

Cov.:

AF XY:

0.0545

AC XY:

4042

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.0120

Gnomad4 AMR

AF:

0.0491

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.000392

Gnomad4 SAS

AF:

0.0162

Gnomad4 FIN

AF:

0.134

Gnomad4 NFE

AF:

0.0747

Gnomad4 OTH

AF:

0.0432

Alfa

AF:

0.0578

Hom.:

Bravo

AF:

0.0454

Asia WGS

AF:

0.00953

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.34

DANN

Benign

0.71

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