Variant rs140685 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000810.4(GABRA5):c.975C>T(p.Ala325Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,584,982 control chromosomes in the GnomAD database, including 166,093 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 17527 hom., cov: 33)

Exomes 𝑓: 0.45 ( 148566 hom. )

Consequence

GABRA5
NM_000810.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.49

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 15-26943312-C-T is Benign according to our data. Variant chr15-26943312-C-T is described in ClinVar as [Benign]. Clinvar id is 1252856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.49 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 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.975C>T	p.Ala325Ala	synonymous_variant	10/11	ENST00000335625.10	NP_000801.1	P31644

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GABRA5	ENST00000335625.10 linkuse as main transcript	c.975C>T	p.Ala325Ala	synonymous_variant	10/11	1	NM_000810.4	ENSP00000335592.5	P31644
GABRA5	ENST00000355395.9 linkuse as main transcript	c.975C>T	p.Ala325Ala	synonymous_variant	9/10	5		ENSP00000347557.5	P31644
GABRA5	ENST00000400081.7 linkuse as main transcript	c.975C>T	p.Ala325Ala	synonymous_variant	10/11	5		ENSP00000382953.3	P31644

Frequencies

GnomAD3 genomes

AF:

0.477

AC:

72444

AN:

151956

Hom.:

17510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.520

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.509

Gnomad ASJ

AF:

0.564

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.408

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.466

Gnomad OTH

AF:

0.489

GnomAD3 exomes

AF:

0.462

AC:

95126

AN:

205864

Hom.:

22365

AF XY:

0.459

AC XY:

50709

AN XY:

110518

show subpopulations

Gnomad AFR exome

AF:

0.527

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.560

Gnomad EAS exome

AF:

0.342

Gnomad SAS exome

AF:

0.411

Gnomad FIN exome

AF:

0.421

Gnomad NFE exome

AF:

0.466

Gnomad OTH exome

AF:

0.473

GnomAD4 exome

AF:

0.453

AC:

649334

AN:

1432908

Hom.:

148566

Cov.:

AF XY:

0.452

AC XY:

320930

AN XY:

710016

show subpopulations

Gnomad4 AFR exome

AF:

0.521

Gnomad4 AMR exome

AF:

0.517

Gnomad4 ASJ exome

AF:

0.560

Gnomad4 EAS exome

AF:

0.328

Gnomad4 SAS exome

AF:

0.412

Gnomad4 FIN exome

AF:

0.418

Gnomad4 NFE exome

AF:

0.454

Gnomad4 OTH exome

AF:

0.467

GnomAD4 genome

AF:

0.477

AC:

72505

AN:

152074

Hom.:

17527

Cov.:

AF XY:

0.474

AC XY:

35263

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.520

Gnomad4 AMR

AF:

0.510

Gnomad4 ASJ

AF:

0.564

Gnomad4 EAS

AF:

0.330

Gnomad4 SAS

AF:

0.399

Gnomad4 FIN

AF:

0.408

Gnomad4 NFE

AF:

0.466

Gnomad4 OTH

AF:

0.493

Alfa

AF:

0.472

Hom.:

27922

Bravo

AF:

0.484

Asia WGS

AF:

0.401

AC:

1393

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 09, 2019	- -

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

-0.60

CADD

Benign

6.7

DANN

Benign

0.89

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