rs5970269

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

GABRA3 Gene-Disease associations (from GenCC):

• epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000808.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA3	NM_000808.4	MANE Select	c.263-29536C>T		intron	N/A	NP_000799.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA3	ENST00000370314.9	TSL:1 MANE Select	c.263-29536C>T		intron	N/A	ENSP00000359337.4
	GABRA3	ENST00000535043.1	TSL:1	c.263-29536C>T		intron	N/A	ENSP00000443527.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 23430 AN: 110382 Hom.: 2275 Cov.: 22

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

African (AFR) AF: 0.385 AC: 11641 AN: 30241

American (AMR) AF: 0.111 AC: 1158 AN: 10419

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 436 AN: 2613

East Asian (EAS) AF: 0.202 AC: 705 AN: 3490

South Asian (SAS) AF: 0.175 AC: 452 AN: 2581

European-Finnish (FIN) AF: 0.168 AC: 982 AN: 5850

Middle Eastern (MID) AF: 0.180 AC: 39 AN: 217

European-Non Finnish (NFE) AF: 0.145 AC: 7681 AN: 52838

Other (OTH) AF: 0.193 AC: 291 AN: 1506

Alfa AF: 0.202 Hom.: 3091

Bravo AF: 0.218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.9
DANN	Benign	0.55
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5970269; hg19: chrX-151482743;