chr5-161895883-G-A

Position:

chr5-161895883-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001127644.2(GABRA1):c.1059+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,601,462 control chromosomes in the GnomAD database, including 336,405 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30064 hom., cov: 32)

Exomes 𝑓: 0.65 ( 306341 hom. )

Consequence

GABRA1
NM_001127644.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.302

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 5-161895883-G-A is Benign according to our data. Variant chr5-161895883-G-A is described in ClinVar as [Benign]. Clinvar id is 93431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-161895883-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.693 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.1059+15G>A		intron_variant		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.1059+15G>A		intron_variant		1	NM_001127644.2	ENSP00000377517	P1

Frequencies

GnomAD3 genomes

AF:

0.625

AC:

95015

AN:

151930

Hom.:

30025

Cov.:

show subpopulations

Gnomad AFR

AF:

0.599

Gnomad AMI

AF:

0.573

Gnomad AMR

AF:

0.704

Gnomad ASJ

AF:

0.647

Gnomad EAS

AF:

0.463

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.554

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.652

Gnomad OTH

AF:

0.625

GnomAD3 exomes

AF:

0.621

AC:

156072

AN:

251212

Hom.:

49256

AF XY:

0.616

AC XY:

83656

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.600

Gnomad AMR exome

AF:

0.716

Gnomad ASJ exome

AF:

0.654

Gnomad EAS exome

AF:

0.439

Gnomad SAS exome

AF:

0.568

Gnomad FIN exome

AF:

0.549

Gnomad NFE exome

AF:

0.650

Gnomad OTH exome

AF:

0.628

GnomAD4 exome

AF:

0.648

AC:

939033

AN:

1449414

Hom.:

306341

Cov.:

AF XY:

0.644

AC XY:

465075

AN XY:

721866

show subpopulations

Gnomad4 AFR exome

AF:

0.595

Gnomad4 AMR exome

AF:

0.714

Gnomad4 ASJ exome

AF:

0.652

Gnomad4 EAS exome

AF:

0.479

Gnomad4 SAS exome

AF:

0.567

Gnomad4 FIN exome

AF:

0.556

Gnomad4 NFE exome

AF:

0.665

Gnomad4 OTH exome

AF:

0.636

GnomAD4 genome

AF:

0.626

AC:

95111

AN:

152048

Hom.:

30064

Cov.:

AF XY:

0.622

AC XY:

46227

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.599

Gnomad4 AMR

AF:

0.704

Gnomad4 ASJ

AF:

0.647

Gnomad4 EAS

AF:

0.463

Gnomad4 SAS

AF:

0.562

Gnomad4 FIN

AF:

0.554

Gnomad4 NFE

AF:

0.652

Gnomad4 OTH

AF:

0.625

Alfa

AF:

0.641

Hom.:

7890

Bravo

AF:

0.634

Asia WGS

AF:

0.531

AC:

1850

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

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 85% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 79. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 03, 2013	- -
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

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

- -

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

-0.85

CADD

Benign

0.96

DANN

Benign

0.17

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