rs6627588

Positions:

• chrX-152425875-A-C

Variant summary

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

The NM_000808.4(GABRA3):​c.-27+25271T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 109,288 control chromosomes in the GnomAD database, including 13,208 homozygotes. There are 16,488 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 0.53 (13208 hom., 16488 hem., cov: 21)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA3	NM_000808.4	c.-27+25271T>G		intron_variant		ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.-27+25271T>G		intron_variant			XP_006724874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA3	ENST00000370314.9	c.-27+25271T>G		intron_variant		1	NM_000808.4	ENSP00000359337.4

Frequencies

GnomAD3 genomes AF: 0.527 AC: 57562 AN: 109226 Hom.: 13215 Cov.: 21 AF XY: 0.522 AC XY: 16467 AN XY: 31536

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.657

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.527 AC: 57559 AN: 109288 Hom.: 13208 Cov.: 21 AF XY: 0.522 AC XY: 16488 AN XY: 31606

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.523

Alfa AF: 0.628 Hom.: 17861

Bravo AF: 0.495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.87
DANN	Benign	0.73

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: rs6627588; hg19: chrX-151594347;