rs2201169

Variant names:

• chrX-152321843-A-G
• rs2201169
• NM_000808.4:c.262+23738T>C

Variant summary

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

The NM_000808.4(GABRA3):​c.262+23738T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 109,528 control chromosomes in the GnomAD database, including 2,279 homozygotes. There are 6,367 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 0.21 (2279 hom., 6367 hem., cov: 22)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 5 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA3	NM_000808.4	c.262+23738T>C		intron_variant	Intron 3 of 9	ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.262+23738T>C		intron_variant	Intron 3 of 8		XP_006724874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA3	ENST00000370314.9	c.262+23738T>C		intron_variant	Intron 3 of 9	1	NM_000808.4	ENSP00000359337.4
GABRA3	ENST00000535043.1	c.262+23738T>C		intron_variant	Intron 3 of 9	1		ENSP00000443527.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 23155 AN: 109479 Hom.: 2279 Cov.: 22

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.212 AC: 23186 AN: 109528 Hom.: 2279 Cov.: 22 AF XY: 0.200 AC XY: 6367 AN XY: 31888

African (AFR) AF: 0.385 AC: 11538 AN: 29946

American (AMR) AF: 0.111 AC: 1147 AN: 10366

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 431 AN: 2596

East Asian (EAS) AF: 0.202 AC: 693 AN: 3439

South Asian (SAS) AF: 0.171 AC: 433 AN: 2529

European-Finnish (FIN) AF: 0.163 AC: 943 AN: 5801

Middle Eastern (MID) AF: 0.189 AC: 40 AN: 212

European-Non Finnish (NFE) AF: 0.145 AC: 7600 AN: 52479

Other (OTH) AF: 0.193 AC: 286 AN: 1485

Alfa AF: 0.190 Hom.: 1236

Bravo AF: 0.219

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.63
PhyloP100		-1.2
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: rs2201169; hg19: chrX-151490315;