Variant rs1078749 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.48T>C(p.Asn16=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 1,601,692 control chromosomes in the GnomAD database, including 1,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 127 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1068 hom. )

Consequence

GNB4
NM_021629.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.655

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=-0.49).

BP6

Variant 3-179426153-A-G is Benign according to our data. Variant chr3-179426153-A-G is described in ClinVar as [Benign]. Clinvar id is 414883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-179426153-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.655 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.128 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.48T>C	p.Asn16=	synonymous_variant	2/10	ENST00000232564.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNB4	ENST00000232564.8 linkuse as main transcript	c.48T>C	p.Asn16=	synonymous_variant	2/10	1	NM_021629.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0348

AC:

5302

AN:

152230

Hom.:

126

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0266

Gnomad AMI

AF:

0.124

Gnomad AMR

AF:

0.0406

Gnomad ASJ

AF:

0.0838

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0203

Gnomad FIN

AF:

0.0200

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.0393

Gnomad OTH

AF:

0.0621

GnomAD3 exomes

AF:

0.0333

AC:

7948

AN:

238918

Hom.:

188

AF XY:

0.0343

AC XY:

4426

AN XY:

129214

show subpopulations

Gnomad AFR exome

AF:

0.0257

Gnomad AMR exome

AF:

0.0306

Gnomad ASJ exome

AF:

0.0773

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0204

Gnomad FIN exome

AF:

0.0227

Gnomad NFE exome

AF:

0.0405

Gnomad OTH exome

AF:

0.0561

GnomAD4 exome

AF:

0.0349

AC:

50648

AN:

1449344

Hom.:

1068

Cov.:

AF XY:

0.0349

AC XY:

25171

AN XY:

720798

show subpopulations

Gnomad4 AFR exome

AF:

0.0266

Gnomad4 AMR exome

AF:

0.0328

Gnomad4 ASJ exome

AF:

0.0769

Gnomad4 EAS exome

AF:

0.0000759

Gnomad4 SAS exome

AF:

0.0209

Gnomad4 FIN exome

AF:

0.0225

Gnomad4 NFE exome

AF:

0.0363

Gnomad4 OTH exome

AF:

0.0413

GnomAD4 genome

AF:

0.0348

AC:

5303

AN:

152348

Hom.:

127

Cov.:

AF XY:

0.0340

AC XY:

2531

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0266

Gnomad4 AMR

AF:

0.0406

Gnomad4 ASJ

AF:

0.0838

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0203

Gnomad4 FIN

AF:

0.0200

Gnomad4 NFE

AF:

0.0393

Gnomad4 OTH

AF:

0.0615

Alfa

AF:

0.0424

Hom.:

225

Bravo

AF:

0.0365

Asia WGS

AF:

0.0120

AC:

AN:

3474

EpiCase

AF:

0.0495

EpiControl

AF:

0.0504

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 30, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Charcot-Marie-Tooth disease dominant intermediate F

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.6

DANN

Benign

0.63

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