rs5925155

chrX-152289446-G-AchrX-152289446-G-CchrX-152289446-G-T

Variant summary

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

The NM_000808.4(GABRA3):c.263-4711C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 107,861 control chromosomes in the GnomAD database, including 10,096 homozygotes. There are 13,404 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 0.45 (10096 hom., 13404 hem., cov: 21)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA3	NM_000808.4	c.263-4711C>T		intron_variant		ENST00000370314.9
GABRA3	XM_006724811.4	c.263-4711C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA3	ENST00000370314.9	c.263-4711C>T		intron_variant		1	NM_000808.4	P1
GABRA3	ENST00000535043.1	c.263-4711C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 48203 AN: 107841 Hom.: 10101 Cov.: 21 AF XY: 0.438 AC XY: 13410 AN XY: 30593

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.447 AC: 48182 AN: 107861 Hom.: 10096 Cov.: 21 AF XY: 0.438 AC XY: 13404 AN XY: 30629

Gnomad4 AFR AF: 0.0983

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.437

Alfa AF: 0.508 Hom.: 12605

Bravo AF: 0.423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.30
Dann	Benign	0.44

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: rs5925155; hg19: chrX-151457918;