rs11135176

Positions:

chr5-162095550-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_198904.4(GABRG2):c.315C>T(p.Asn105=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 1,598,584 control chromosomes in the GnomAD database, including 10,705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 884 hom., cov: 32)

Exomes 𝑓: 0.098 ( 9821 hom. )

Consequence

GABRG2
NM_198904.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.284

Variant links:

Genes affected

GABRG2 (HGNC:4087): (gamma-aminobutyric acid type A receptor subunit gamma2) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammlian brain, where it acts at GABA-A receptors, which are ligand-gated chloride channels. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene have been associated with epilepsy and febrile seizures. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

GABRG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 5-162095550-C-T is Benign according to our data. Variant chr5-162095550-C-T is described in ClinVar as [Benign]. Clinvar id is 129127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.284 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG2	NM_198904.4 linkuse as main transcript	c.315C>T	p.Asn105=	synonymous_variant	3/10	ENST00000639213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG2	ENST00000639213.2 linkuse as main transcript	c.315C>T	p.Asn105=	synonymous_variant	3/10	1	NM_198904.4	A1	P18507-2

Frequencies

GnomAD3 genomes

AF:

0.0841

AC:

12774

AN:

151980

Hom.:

872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0196

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.0369

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.0808

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0817

Gnomad OTH

AF:

0.0699

GnomAD3 exomes

AF:

0.130

AC:

32325

AN:

248550

Hom.:

3386

AF XY:

0.125

AC XY:

16788

AN XY:

134336

show subpopulations

Gnomad AFR exome

AF:

0.0176

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.0382

Gnomad EAS exome

AF:

0.213

Gnomad SAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.0806

Gnomad NFE exome

AF:

0.0776

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.0985

AC:

142433

AN:

1446486

Hom.:

9821

Cov.:

AF XY:

0.100

AC XY:

72102

AN XY:

720464

show subpopulations

Gnomad4 AFR exome

AF:

0.0151

Gnomad4 AMR exome

AF:

0.307

Gnomad4 ASJ exome

AF:

0.0405

Gnomad4 EAS exome

AF:

0.256

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.0835

Gnomad4 NFE exome

AF:

0.0827

Gnomad4 OTH exome

AF:

0.0942

GnomAD4 genome

AF:

0.0841

AC:

12795

AN:

152098

Hom.:

884

Cov.:

AF XY:

0.0888

AC XY:

6598

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0196

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.0369

Gnomad4 EAS

AF:

0.227

Gnomad4 SAS

AF:

0.204

Gnomad4 FIN

AF:

0.0808

Gnomad4 NFE

AF:

0.0817

Gnomad4 OTH

AF:

0.0720

Alfa

AF:

0.0775

Hom.:

795

Bravo

AF:

0.0893

Asia WGS

AF:

0.227

AC:

789

AN:

3476

EpiCase

AF:

0.0796

EpiControl

AF:

0.0680

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 32% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 30. Only high quality variants are reported. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 13, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Febrile seizures, familial, 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Apr 28, 2017

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Epilepsy, childhood absence 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Epilepsy, childhood absence 2;C1969810:Febrile seizures, familial, 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

0.43

DANN

Benign

0.64

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