rs5970269

Variant names:

• chrX-152314271-G-A
• rs5970269
• NM_000808.4:c.263-29536C>T

Variant summary

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

The NM_000808.4(GABRA3):​c.263-29536C>T 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 110,434 control chromosomes in the GnomAD database, including 2,275 homozygotes. There are 6,649 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 (2275 hom., 6649 hem., cov: 22)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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=-0.76).
• 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.263-29536C>T		intron_variant	Intron 3 of 9	ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.263-29536C>T		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.263-29536C>T		intron_variant	Intron 3 of 9	1	NM_000808.4	ENSP00000359337.4
GABRA3	ENST00000535043.1	c.263-29536C>T		intron_variant	Intron 3 of 9	1		ENSP00000443527.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 23430 AN: 110382 Hom.: 2275 Cov.: 22 AF XY: 0.202 AC XY: 6612 AN XY: 32714

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.172

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: 23464 AN: 110434 Hom.: 2275 Cov.: 22 AF XY: 0.203 AC XY: 6649 AN XY: 32776

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.193

Alfa AF: 0.190 Hom.: 1425

Bravo AF: 0.218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.9
DANN	Benign	0.55

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: rs5970269; hg19: chrX-151482743;