rs6627221

Positions:

• chrX-152247402-T-C

Variant summary

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

The ENST00000370314.9(GABRA3):​c.551+8376A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 110,134 control chromosomes in the GnomAD database, including 3,562 homozygotes. There are 8,690 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 0.27 (3562 hom., 8690 hem., cov: 22)
• Consequence: GABRA3 ENST00000370314.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA3	NM_000808.4	c.551+8376A>G		intron_variant		ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.551+8376A>G		intron_variant			XP_006724874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA3	ENST00000370314.9	c.551+8376A>G		intron_variant		1	NM_000808.4	ENSP00000359337	P1
GABRA3	ENST00000535043.1	c.551+8376A>G		intron_variant		1		ENSP00000443527	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 30134 AN: 110081 Hom.: 3558 Cov.: 22 AF XY: 0.266 AC XY: 8644 AN XY: 32461

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.274 AC: 30181 AN: 110134 Hom.: 3562 Cov.: 22 AF XY: 0.267 AC XY: 8690 AN XY: 32524

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.256

Alfa AF: 0.214 Hom.: 2078

Bravo AF: 0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.7
DANN	Benign	0.76

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: rs6627221; hg19: chrX-151415874;