rs76812964

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000814.6(GABRB3):c.783G>A(p.Ser261Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 1,613,916 control chromosomes in the GnomAD database, including 854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 52 hom., cov: 33)

Exomes 𝑓: 0.030 ( 802 hom. )

Consequence

GABRB3
NM_000814.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.47

Variant links:

Genes affected

GABRB3 (HGNC:4083): (gamma-aminobutyric acid type A receptor subunit beta3) This gene encodes a member of the ligand-gated ionic channel family. The encoded protein is one the subunits of a multi-subunit chloride channel that serves as the receptor for gamma-aminobutyric acid, a major inhibitory neurotransmitter of the mammalian nervous system. This gene is located on the long arm of chromosome 15 in a cluster with two other genes encoding related subunits of the family. This gene may be associated with the pathogenesis of several disorders including Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2013]

GABRB3 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=-0.85).

BP6

Variant 15-26567633-C-T is Benign according to our data. Variant chr15-26567633-C-T is described in ClinVar as [Benign]. Clinvar id is 256821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-26567633-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.47 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0225 (3430/152242) while in subpopulation NFE AF= 0.0325 (2210/68016). AF 95% confidence interval is 0.0314. There are 52 homozygotes in gnomad4. There are 1626 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3430 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB3	NM_000814.6 link	c.783G>A	p.Ser261Ser	synonymous_variant	Exon 7 of 9	ENST00000311550.10	NP_000805.1	P28472-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000311550.10 link	c.783G>A	p.Ser261Ser	synonymous_variant	Exon 7 of 9	1	NM_000814.6	ENSP00000308725.5		P28472-1

Frequencies

GnomAD3 genomes

AF:

0.0225

AC:

3427

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00577

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0217

Gnomad ASJ

AF:

0.0447

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.0387

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0325

Gnomad OTH

AF:

0.0259

GnomAD3 exomes

AF:

0.0247

AC:

6219

AN:

251310

Hom.:

113

AF XY:

0.0249

AC XY:

3384

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00591

Gnomad AMR exome

AF:

0.0174

Gnomad ASJ exome

AF:

0.0457

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00751

Gnomad FIN exome

AF:

0.0367

Gnomad NFE exome

AF:

0.0342

Gnomad OTH exome

AF:

0.0253

GnomAD4 exome

AF:

0.0305

AC:

44525

AN:

1461674

Hom.:

802

Cov.:

AF XY:

0.0297

AC XY:

21609

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00469

Gnomad4 AMR exome

AF:

0.0181

Gnomad4 ASJ exome

AF:

0.0470

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00670

Gnomad4 FIN exome

AF:

0.0354

Gnomad4 NFE exome

AF:

0.0344

Gnomad4 OTH exome

AF:

0.0252

GnomAD4 genome

AF:

0.0225

AC:

3430

AN:

152242

Hom.:

Cov.:

AF XY:

0.0218

AC XY:

1626

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00575

Gnomad4 AMR

AF:

0.0217

Gnomad4 ASJ

AF:

0.0447

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.0387

Gnomad4 NFE

AF:

0.0325

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.0307

Hom.:

Bravo

AF:

0.0213

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0320

EpiControl

AF:

0.0334

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 26, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Epilepsy, childhood absence, susceptibility to, 1;C2677087:Epilepsy, childhood absence, susceptibility to, 5

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Seizure

Benign:1

Apr 11, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.54

DANN

Benign

0.43

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