chrX-152428729-A-G

Position:

• chrX-152428729-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.79).
• 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/exons	MANE	Protein	UniProt
GABRA3	NM_000808.4	c.-27+22417T>C		intron_variant		ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.-27+22417T>C		intron_variant			XP_006724874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA3	ENST00000370314.9	c.-27+22417T>C		intron_variant		1	NM_000808.4	ENSP00000359337	P1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 17527 AN: 110797 Hom.: 1062 Cov.: 23 AF XY: 0.153 AC XY: 5044 AN XY: 33035

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

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.153

Alfa AF: 0.161 Hom.: 1080

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

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: rs3902802; hg19: chrX-151597201;