Variant rs140683 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_000810.4(GABRA5):c.878-27T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,533,578 control chromosomes in the GnomAD database, including 144,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.37 ( 10921 hom., cov: 34)

Exomes 𝑓: 0.43 ( 133787 hom. )

Consequence

GABRA5
NM_000810.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.129

Variant links:

Genes affected

GABRA5 (HGNC:4079): (gamma-aminobutyric acid type A receptor subunit alpha5) 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. At least 16 distinct subunits of GABA-A receptors have been identified. Transcript variants utilizing three different alternative non-coding first exons have been described. [provided by RefSeq, Jul 2008]

GABRA5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 15-26943188-T-A is Benign according to our data. Variant chr15-26943188-T-A is described in ClinVar as [Benign]. Clinvar id is 1285289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA5	NM_000810.4 linkuse as main transcript	c.878-27T>A		intron_variant		ENST00000335625.10	NP_000801.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
GABRA5	ENST00000335625.10 linkuse as main transcript	c.878-27T>A	intron_variant	1	NM_000810.4	ENSP00000335592	P1
GABRA5	ENST00000355395.9 linkuse as main transcript	c.878-27T>A	intron_variant	5		ENSP00000347557	P1
GABRA5	ENST00000400081.7 linkuse as main transcript	c.878-27T>A	intron_variant	5		ENSP00000382953	P1

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55925

AN:

152032

Hom.:

10927

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.563

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.354

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.445

Gnomad OTH

AF:

0.355

GnomAD3 exomes

AF:

0.369

AC:

53836

AN:

145890

Hom.:

10651

AF XY:

0.373

AC XY:

28965

AN XY:

77650

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.280

Gnomad ASJ exome

AF:

0.362

Gnomad EAS exome

AF:

0.191

Gnomad SAS exome

AF:

0.358

Gnomad FIN exome

AF:

0.421

Gnomad NFE exome

AF:

0.451

Gnomad OTH exome

AF:

0.390

GnomAD4 exome

AF:

0.435

AC:

600267

AN:

1381430

Hom.:

133787

Cov.:

AF XY:

0.433

AC XY:

295013

AN XY:

680658

show subpopulations

Gnomad4 AFR exome

AF:

0.251

Gnomad4 AMR exome

AF:

0.293

Gnomad4 ASJ exome

AF:

0.359

Gnomad4 EAS exome

AF:

0.201

Gnomad4 SAS exome

AF:

0.361

Gnomad4 FIN exome

AF:

0.426

Gnomad4 NFE exome

AF:

0.462

Gnomad4 OTH exome

AF:

0.402

GnomAD4 genome

AF:

0.368

AC:

55936

AN:

152148

Hom.:

10921

Cov.:

AF XY:

0.364

AC XY:

27093

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.253

Gnomad4 AMR

AF:

0.350

Gnomad4 ASJ

AF:

0.359

Gnomad4 EAS

AF:

0.200

Gnomad4 SAS

AF:

0.355

Gnomad4 FIN

AF:

0.429

Gnomad4 NFE

AF:

0.445

Gnomad4 OTH

AF:

0.353

Alfa

AF:

0.397

Hom.:

2281

Bravo

AF:

0.357

Asia WGS

AF:

0.281

AC:

980

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Developmental and epileptic encephalopathy, 79

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

-0.81

CADD

Benign

6.6

DANN

Benign

0.53

BranchPoint Hunter

1.0

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