rs5925196

Positions:

• chrX-152644427-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018558.4(GABRQ):​c.239-1100T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 112,026 control chromosomes in the GnomAD database, including 825 homozygotes. There are 4,240 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 0.13 (825 hom., 4240 hem., cov: 24)
• Consequence: GABRQ NM_018558.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.18

Genes affected

GABRQ (HGNC:14454): (gamma-aminobutyric acid type A receptor subunit theta) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes the theta subunit of the GABA A receptor. The gene is mapped to chromosome Xq28 in a cluster of genes including those that encode the alpha 3 and epsilon subunits of the GABA A receptor. [provided by RefSeq, Jul 2017]

MAGEA3-DT (HGNC:56247): (MAGEA3 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRQ	NM_018558.4	c.239-1100T>A		intron_variant		ENST00000598523.3	NP_061028.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRQ	ENST00000598523.3	c.239-1100T>A		intron_variant		1	NM_018558.4	ENSP00000469332.1
MAGEA3-DT	ENST00000671457.1	n.130-4633A>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.131 AC: 14704 AN: 111971 Hom.: 825 Cov.: 24 AF XY: 0.124 AC XY: 4239 AN XY: 34179

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.0742

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0400

Gnomad SAS AF: 0.0787

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.131 AC: 14700 AN: 112026 Hom.: 825 Cov.: 24 AF XY: 0.124 AC XY: 4240 AN XY: 34244

Gnomad4 AFR AF: 0.0569

Gnomad4 AMR AF: 0.0738

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.0398

Gnomad4 SAS AF: 0.0792

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.123

Alfa AF: 0.163 Hom.: 968

Bravo AF: 0.119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.72

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: rs5925196; hg19: chrX-151812888;