rs3902802

Variant names:

• chrX-152428729-A-G
• rs3902802
• NM_000808.4:c.-27+22417T>C

Variant summary

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

The NM_000808.4(GABRA3):​c.-27+22417T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 110,855 control chromosomes in the GnomAD database, including 1,061 homozygotes. There are 5,057 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 0.16 (1061 hom., 5057 hem., cov: 23)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA3	NM_000808.4	c.-27+22417T>C		intron_variant	Intron 1 of 9	ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.-27+22417T>C		intron_variant	Intron 1 of 8		XP_006724874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA3	ENST00000370314.9	c.-27+22417T>C		intron_variant	Intron 1 of 9	1	NM_000808.4	ENSP00000359337.4

Frequencies

GnomAD3 genomes AF: 0.158 AC: 17527 AN: 110797 Hom.: 1062 Cov.: 23

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.158 AC: 17545 AN: 110855 Hom.: 1061 Cov.: 23 AF XY: 0.153 AC XY: 5057 AN XY: 33103

African (AFR) AF: 0.219 AC: 6674 AN: 30455

American (AMR) AF: 0.134 AC: 1387 AN: 10356

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 288 AN: 2644

East Asian (EAS) AF: 0.119 AC: 417 AN: 3503

South Asian (SAS) AF: 0.171 AC: 448 AN: 2619

European-Finnish (FIN) AF: 0.151 AC: 887 AN: 5884

Middle Eastern (MID) AF: 0.193 AC: 41 AN: 212

European-Non Finnish (NFE) AF: 0.134 AC: 7093 AN: 52990

Other (OTH) AF: 0.153 AC: 231 AN: 1511

Alfa AF: 0.162 Hom.: 2260

Bravo AF: 0.160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.2
DANN	Benign	0.61
PhyloP100		0.33
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: rs3902802; hg19: chrX-151597201;