X-152378770-C-T

Variant names:

• chrX-152378770-C-T
• rs4828694
• NM_000808.4:c.-26-14174G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000808.4(GABRA3):​c.-26-14174G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 109,989 control chromosomes in the GnomAD database, including 5,308 homozygotes. There are 11,602 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 0.36 (5308 hom., 11602 hem., cov: 23)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.427 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA3	NM_000808.4	MANE Select	c.-26-14174G>A		intron	N/A	NP_000799.1	P34903

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA3	ENST00000370314.9	TSL:1 MANE Select	c.-26-14174G>A		intron	N/A	ENSP00000359337.4	P34903
	GABRA3	ENST00000535043.1	TSL:1	c.-27+10536G>A		intron	N/A	ENSP00000443527.1	P34903
	GABRA3	ENST00000862742.1		c.-27+4542G>A		intron	N/A	ENSP00000532801.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 39937 AN: 109937 Hom.: 5301 Cov.: 23

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.432

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.363 AC: 39952 AN: 109989 Hom.: 5308 Cov.: 23 AF XY: 0.358 AC XY: 11602 AN XY: 32405

African (AFR) AF: 0.380 AC: 11554 AN: 30367

American (AMR) AF: 0.438 AC: 4525 AN: 10329

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 908 AN: 2624

East Asian (EAS) AF: 0.305 AC: 1067 AN: 3504

South Asian (SAS) AF: 0.387 AC: 1019 AN: 2632

European-Finnish (FIN) AF: 0.327 AC: 1834 AN: 5617

Middle Eastern (MID) AF: 0.417 AC: 86 AN: 206

European-Non Finnish (NFE) AF: 0.348 AC: 18292 AN: 52557

Other (OTH) AF: 0.367 AC: 544 AN: 1483

Alfa AF: 0.359 Hom.: 2685

Bravo AF: 0.370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.35
DANN	Benign	0.50
PhyloP100		-0.25
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: rs4828694; hg19: chrX-151547242;