Variant rs2290732 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_001127644.2(GABRA1):c.*470A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.598 in 154,248 control chromosomes in the GnomAD database, including 28,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.60 ( 27556 hom., cov: 31)

Exomes 𝑓: 0.60 ( 471 hom. )

Consequence

GABRA1
NM_001127644.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.31

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 5-161897892-A-G is Benign according to our data. Variant chr5-161897892-A-G is described in ClinVar as [Benign]. Clinvar id is 352608.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.673 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.*470A>G		3_prime_UTR_variant	10/10	ENST00000393943.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA1	ENST00000393943.10 linkuse as main transcript	c.*470A>G		3_prime_UTR_variant	10/10	1	NM_001127644.2	P1

Frequencies

GnomAD3 genomes

AF:

0.598

AC:

90725

AN:

151682

Hom.:

27520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.562

Gnomad AMI

AF:

0.533

Gnomad AMR

AF:

0.683

Gnomad ASJ

AF:

0.589

Gnomad EAS

AF:

0.462

Gnomad SAS

AF:

0.551

Gnomad FIN

AF:

0.538

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.626

Gnomad OTH

AF:

0.592

GnomAD4 exome

AF:

0.599

AC:

1464

AN:

2446

Hom.:

471

Cov.:

AF XY:

0.605

AC XY:

811

AN XY:

1340

show subpopulations

Gnomad4 AFR exome

AF:

0.417

Gnomad4 AMR exome

AF:

0.678

Gnomad4 ASJ exome

AF:

0.423

Gnomad4 EAS exome

AF:

0.333

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.613

Gnomad4 OTH exome

AF:

0.597

GnomAD4 genome

AF:

0.598

AC:

90816

AN:

151802

Hom.:

27556

Cov.:

AF XY:

0.596

AC XY:

44189

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.562

Gnomad4 AMR

AF:

0.684

Gnomad4 ASJ

AF:

0.589

Gnomad4 EAS

AF:

0.462

Gnomad4 SAS

AF:

0.553

Gnomad4 FIN

AF:

0.538

Gnomad4 NFE

AF:

0.626

Gnomad4 OTH

AF:

0.593

Alfa

AF:

0.624

Hom.:

10606

Bravo

AF:

0.605

Asia WGS

AF:

0.526

AC:

1827

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Epilepsy, idiopathic generalized, susceptibility to, 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.88

Splicing

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