rs2201169

chrX-152321843-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GABRA3	NM_000808.4	c.262+23738T>C		intron_variant		ENST00000370314.9
GABRA3	XM_006724811.4	c.262+23738T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA3	ENST00000370314.9	c.262+23738T>C		intron_variant		1	NM_000808.4	P1
GABRA3	ENST00000535043.1	c.262+23738T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 23155 AN: 109479 Hom.: 2279 Cov.: 22 AF XY: 0.199 AC XY: 6333 AN XY: 31829

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

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.193

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

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

Other links and lift over

dbSNP: rs2201169; hg19: chrX-151490315;