rs5970223

Positions:

• chrX-152191507-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000808.4(GABRA3):​c.932-1566A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.33 (5023 hom., 9542 hem., cov: 20)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA3	NM_000808.4	c.932-1566A>C		intron_variant		ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.931+6126A>C		intron_variant			XP_006724874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA3	ENST00000370314.9	c.932-1566A>C		intron_variant		1	NM_000808.4	ENSP00000359337.4
GABRA3	ENST00000535043.1	c.932-1566A>C		intron_variant		1		ENSP00000443527.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 35792 AN: 108149 Hom.: 5023 Cov.: 20 AF XY: 0.311 AC XY: 9504 AN XY: 30591

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.331 AC: 35825 AN: 108203 Hom.: 5023 Cov.: 20 AF XY: 0.311 AC XY: 9542 AN XY: 30655

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.320

Alfa AF: 0.277 Hom.: 11619

Bravo AF: 0.351

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.68

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: rs5970223; hg19: chrX-151359979;