Variant 5-161895648-T-C 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_001127644.2(GABRA1):c.857-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 1,595,954 control chromosomes in the GnomAD database, including 3,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 351 hom., cov: 31)

Exomes 𝑓: 0.064 ( 3136 hom. )

Consequence

GABRA1
NM_001127644.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.28

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:

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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 5-161895648-T-C is Benign according to our data. Variant chr5-161895648-T-C is described in ClinVar as [Benign]. Clinvar id is 256816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA1	NM_001127644.2 linkuse as main transcript	c.857-18T>C		intron_variant		ENST00000393943.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA1	ENST00000393943.10 linkuse as main transcript	c.857-18T>C		intron_variant		1	NM_001127644.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0631

AC:

9438

AN:

149568

Hom.:

344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0519

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0824

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.0858

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0447

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0599

Gnomad OTH

AF:

0.0733

GnomAD3 exomes

AF:

0.0922

AC:

18562

AN:

201228

Hom.:

785

AF XY:

0.0936

AC XY:

10134

AN XY:

108226

show subpopulations

Gnomad AFR exome

AF:

0.0635

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.0948

Gnomad SAS exome

AF:

0.120

Gnomad FIN exome

AF:

0.0657

Gnomad NFE exome

AF:

0.0806

Gnomad OTH exome

AF:

0.0934

GnomAD4 exome

AF:

0.0637

AC:

92186

AN:

1446288

Hom.:

3136

Cov.:

AF XY:

0.0651

AC XY:

46812

AN XY:

719592

show subpopulations

Gnomad4 AFR exome

AF:

0.0560

Gnomad4 AMR exome

AF:

0.100

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.0518

Gnomad4 NFE exome

AF:

0.0567

Gnomad4 OTH exome

AF:

0.0696

GnomAD4 genome

AF:

0.0632

AC:

9459

AN:

149666

Hom.:

351

Cov.:

AF XY:

0.0643

AC XY:

4705

AN XY:

73142

show subpopulations

Gnomad4 AFR

AF:

0.0519

Gnomad4 AMR

AF:

0.0824

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.0860

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.0447

Gnomad4 NFE

AF:

0.0599

Gnomad4 OTH

AF:

0.0788

Alfa

AF:

0.0384

Hom.:

Bravo

AF:

0.0673

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.0

DANN

Benign

0.52

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