Variant rs140682 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.606T>C(p.Val202Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 1,613,496 control chromosomes in the GnomAD database, including 281,639 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 31586 hom., cov: 33)

Exomes 𝑓: 0.58 ( 250053 hom. )

Consequence

GABRA5
NM_000810.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.209

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:

GABRB3 (HGNC:4083): (gamma-aminobutyric acid type A receptor subunit beta3) This gene encodes a member of the ligand-gated ionic channel family. The encoded protein is one the subunits of a multi-subunit chloride channel that serves as the receptor for gamma-aminobutyric acid, a major inhibitory neurotransmitter of the mammalian nervous system. This gene is located on the long arm of chromosome 15 in a cluster with two other genes encoding related subunits of the family. This gene may be associated with the pathogenesis of several disorders including Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2013]

GABRB3 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=-0.61).

BP6

Variant 15-26937210-T-C is Benign according to our data. Variant chr15-26937210-T-C is described in ClinVar as [Benign]. Clinvar id is 1285288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.209 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.795 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.606T>C	p.Val202Val	synonymous_variant	8/11	ENST00000335625.10	NP_000801.1	P31644

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA5	ENST00000335625.10 linkuse as main transcript	c.606T>C	p.Val202Val	synonymous_variant	8/11	1	NM_000810.4	ENSP00000335592.5		P31644

Frequencies

GnomAD3 genomes

AF:

0.634

AC:

96402

AN:

152012

Hom.:

31530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.802

Gnomad AMI

AF:

0.646

Gnomad AMR

AF:

0.534

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.675

Gnomad SAS

AF:

0.592

Gnomad FIN

AF:

0.657

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.560

Gnomad OTH

AF:

0.596

GnomAD3 exomes

AF:

0.586

AC:

145971

AN:

249264

Hom.:

43813

AF XY:

0.583

AC XY:

78892

AN XY:

135226

show subpopulations

Gnomad AFR exome

AF:

0.811

Gnomad AMR exome

AF:

0.495

Gnomad ASJ exome

AF:

0.486

Gnomad EAS exome

AF:

0.660

Gnomad SAS exome

AF:

0.588

Gnomad FIN exome

AF:

0.651

Gnomad NFE exome

AF:

0.567

Gnomad OTH exome

AF:

0.568

GnomAD4 exome

AF:

0.582

AC:

850623

AN:

1461366

Hom.:

250053

Cov.:

AF XY:

0.581

AC XY:

422368

AN XY:

726996

show subpopulations

Gnomad4 AFR exome

AF:

0.817

Gnomad4 AMR exome

AF:

0.501

Gnomad4 ASJ exome

AF:

0.487

Gnomad4 EAS exome

AF:

0.680

Gnomad4 SAS exome

AF:

0.585

Gnomad4 FIN exome

AF:

0.648

Gnomad4 NFE exome

AF:

0.574

Gnomad4 OTH exome

AF:

0.579

GnomAD4 genome

AF:

0.634

AC:

96512

AN:

152130

Hom.:

31586

Cov.:

AF XY:

0.634

AC XY:

47177

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.803

Gnomad4 AMR

AF:

0.534

Gnomad4 ASJ

AF:

0.482

Gnomad4 EAS

AF:

0.676

Gnomad4 SAS

AF:

0.593

Gnomad4 FIN

AF:

0.657

Gnomad4 NFE

AF:

0.560

Gnomad4 OTH

AF:

0.592

Alfa

AF:

0.595

Hom.:

14537

Bravo

AF:

0.636

Asia WGS

AF:

0.632

AC:

2200

AN:

3478

EpiCase

AF:

0.552

EpiControl

AF:

0.560

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

-0.61

CADD

Benign

1.2

DANN

Benign

0.62

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