X-152351840-A-G

Position:

• chrX-152351840-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.141-6138T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 110,600 control chromosomes in the GnomAD database, including 682 homozygotes. There are 3,781 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 0.12 (682 hom., 3781 hem., cov: 22)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA3	NM_000808.4	c.141-6138T>C		intron_variant		ENST00000370314.9
GABRA3	XM_006724811.4	c.141-6138T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA3	ENST00000370314.9	c.141-6138T>C		intron_variant		1	NM_000808.4	P1
GABRA3	ENST00000535043.1	c.141-6138T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 13394 AN: 110548 Hom.: 682 Cov.: 22 AF XY: 0.115 AC XY: 3769 AN XY: 32864

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0636

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.0755

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0936

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.121 AC: 13406 AN: 110600 Hom.: 682 Cov.: 22 AF XY: 0.115 AC XY: 3781 AN XY: 32924

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0635

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.0754

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0474 Hom.: 227

Bravo AF: 0.121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.67
DANN	Benign	0.73

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: rs11797836; hg19: chrX-151520312;