Variant X-152189723-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000808.4(GABRA3):c.1143+7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00599 in 1,182,383 control chromosomes in the GnomAD database, including 20 homozygotes. There are 2,266 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 2 hom., 176 hem., cov: 22)

Exomes 𝑓: 0.0061 ( 18 hom. 2090 hem. )

Consequence

GABRA3
NM_000808.4 splice_region, intron

Scores

Splicing: ADA: 0.0001531

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.177

Variant links:

Genes affected

GABRA3 (HGNC:4077): (gamma-aminobutyric acid type A receptor subunit alpha3) 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. [provided by RefSeq, Jul 2008]

GABRA3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

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

BP6

Variant X-152189723-A-G is Benign according to our data. Variant chrX-152189723-A-G is described in ClinVar as [Benign]. Clinvar id is 713930.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA3	NM_000808.4 linkuse as main transcript	c.1143+7T>C		splice_region_variant, intron_variant		ENST00000370314.9
GABRA3	XM_006724811.4 linkuse as main transcript	c.931+7910T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
GABRA3	ENST00000370314.9 linkuse as main transcript	c.1143+7T>C	splice_region_variant, intron_variant	1	NM_000808.4	P1
GABRA3	ENST00000535043.1 linkuse as main transcript	c.1143+7T>C	splice_region_variant, intron_variant	1		P1
GABRA3	ENST00000497894.1 linkuse as main transcript	n.214+7T>C	splice_region_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00502

AC:

554

AN:

110464

Hom.:

Cov.:

AF XY:

0.00537

AC XY:

176

AN XY:

32752

show subpopulations

Gnomad AFR

AF:

0.000660

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00192

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00239

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.00688

Gnomad OTH

AF:

0.00546

GnomAD3 exomes

AF:

0.00588

AC:

1044

AN:

177441

Hom.:

AF XY:

0.00626

AC XY:

391

AN XY:

62425

show subpopulations

Gnomad AFR exome

AF:

0.000993

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00193

Gnomad FIN exome

AF:

0.0219

Gnomad NFE exome

AF:

0.00743

Gnomad OTH exome

AF:

0.00600

GnomAD4 exome

AF:

0.00609

AC:

6531

AN:

1071865

Hom.:

Cov.:

AF XY:

0.00612

AC XY:

2090

AN XY:

341589

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.0000525

Gnomad4 EAS exome

AF:

0.0000665

Gnomad4 SAS exome

AF:

0.00136

Gnomad4 FIN exome

AF:

0.0202

Gnomad4 NFE exome

AF:

0.00653

Gnomad4 OTH exome

AF:

0.00428

GnomAD4 genome

AF:

0.00501

AC:

554

AN:

110518

Hom.:

Cov.:

AF XY:

0.00536

AC XY:

176

AN XY:

32816

show subpopulations

Gnomad4 AFR

AF:

0.000659

Gnomad4 AMR

AF:

0.00192

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00239

Gnomad4 FIN

AF:

0.0228

Gnomad4 NFE

AF:

0.00688

Gnomad4 OTH

AF:

0.00538

Alfa

AF:

0.00553

Hom.:

Bravo

AF:

0.00351

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

GABRA3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 11, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.94

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

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