5-161854239-T-C

Position:

chr5-161854239-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001127644.2(GABRA1):c.156T>C(p.Gly52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,596,510 control chromosomes in the GnomAD database, including 55,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4775 hom., cov: 32)

Exomes 𝑓: 0.26 ( 51195 hom. )

Consequence

GABRA1
NM_001127644.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.550

Variant links:

Genes affected

GABRA1 (HGNC:4075): (gamma-aminobutyric acid type A receptor subunit alpha1) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene cause juvenile myoclonic epilepsy and childhood absence epilepsy type 4. Multiple transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

GABRA1 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=-0.52).

BP6

Variant 5-161854239-T-C is Benign according to our data. Variant chr5-161854239-T-C is described in ClinVar as [Benign]. Clinvar id is 129123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.55 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA1	NM_001127644.2 linkuse as main transcript	c.156T>C	p.Gly52=	synonymous_variant	3/10	ENST00000393943.10	NP_001121116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA1	ENST00000393943.10 linkuse as main transcript	c.156T>C	p.Gly52=	synonymous_variant	3/10	1	NM_001127644.2	ENSP00000377517	P1

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36136

AN:

151328

Hom.:

4770

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.385

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.268

Gnomad EAS

AF:

0.302

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.359

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.260

GnomAD3 exomes

AF:

0.264

AC:

66172

AN:

250770

Hom.:

9074

AF XY:

0.268

AC XY:

36350

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.127

Gnomad AMR exome

AF:

0.218

Gnomad ASJ exome

AF:

0.256

Gnomad EAS exome

AF:

0.308

Gnomad SAS exome

AF:

0.256

Gnomad FIN exome

AF:

0.352

Gnomad NFE exome

AF:

0.276

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.263

AC:

380104

AN:

1445064

Hom.:

51195

Cov.:

AF XY:

0.264

AC XY:

190202

AN XY:

719828

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.220

Gnomad4 ASJ exome

AF:

0.256

Gnomad4 EAS exome

AF:

0.287

Gnomad4 SAS exome

AF:

0.257

Gnomad4 FIN exome

AF:

0.350

Gnomad4 NFE exome

AF:

0.264

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.239

AC:

36146

AN:

151446

Hom.:

4775

Cov.:

AF XY:

0.242

AC XY:

17906

AN XY:

74010

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.239

Gnomad4 ASJ

AF:

0.268

Gnomad4 EAS

AF:

0.303

Gnomad4 SAS

AF:

0.266

Gnomad4 FIN

AF:

0.359

Gnomad4 NFE

AF:

0.276

Gnomad4 OTH

AF:

0.262

Alfa

AF:

0.258

Hom.:

2776

Bravo

AF:

0.224

Asia WGS

AF:

0.275

AC:

954

AN:

3478

EpiCase

AF:

0.278

EpiControl

AF:

0.286

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 29, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 27, 2013	- -
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 43% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 40. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 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. -

Idiopathic generalized epilepsy;C1970160:Epilepsy, childhood absence 4;C4013473:Epilepsy, idiopathic generalized, susceptibility to, 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Epilepsy, idiopathic generalized, susceptibility to, 13

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. -

Developmental and epileptic encephalopathy, 19

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.2

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