rs2131190

Variant names:

• chrX-152245827-C-T
• rs2131190
• NM_000808.4:c.551+9951G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000808.4(GABRA3):​c.551+9951G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 110,979 control chromosomes in the GnomAD database, including 734 homozygotes. There are 4,263 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (734 hom., 4263 hem., cov: 23)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.926
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA3	NM_000808.4	c.551+9951G>A		intron_variant	Intron 5 of 9	ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.551+9951G>A		intron_variant	Intron 5 of 8		XP_006724874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA3	ENST00000370314.9	c.551+9951G>A		intron_variant	Intron 5 of 9	1	NM_000808.4	ENSP00000359337.4
GABRA3	ENST00000535043.1	c.551+9951G>A		intron_variant	Intron 5 of 9	1		ENSP00000443527.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 14025 AN: 110927 Hom.: 731 Cov.: 23

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0779

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.123

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 14039 AN: 110979 Hom.: 734 Cov.: 23 AF XY: 0.128 AC XY: 4263 AN XY: 33265

African (AFR) AF: 0.0681 AC: 2086 AN: 30642

American (AMR) AF: 0.220 AC: 2281 AN: 10370

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 421 AN: 2637

East Asian (EAS) AF: 0.0776 AC: 272 AN: 3504

South Asian (SAS) AF: 0.200 AC: 524 AN: 2623

European-Finnish (FIN) AF: 0.154 AC: 920 AN: 5974

Middle Eastern (MID) AF: 0.125 AC: 27 AN: 216

European-Non Finnish (NFE) AF: 0.134 AC: 7083 AN: 52825

Other (OTH) AF: 0.121 AC: 184 AN: 1520

Alfa AF: 0.139 Hom.: 4192

Bravo AF: 0.132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.46
PhyloP100		0.93
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2131190; hg19: chrX-151414299;