rs5924752

chrX-152649506-G-C

Variant summary

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

The NM_018558.4(GABRQ):c.610+173G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 111,452 control chromosomes in the GnomAD database, including 621 homozygotes. There are 3,531 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 0.11 (621 hom., 3531 hem., cov: 23)
• Consequence: GABRQ NM_018558.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRQ	NM_018558.4	c.610+173G>C		intron_variant		ENST00000598523.3
MAGEA3-DT	XR_938525.3	n.157-9712C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRQ	ENST00000598523.3	c.610+173G>C		intron_variant		1	NM_018558.4	P1
MAGEA3-DT	ENST00000671457.1	n.130-9712C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.111 AC: 12333 AN: 111399 Hom.: 622 Cov.: 23 AF XY: 0.105 AC XY: 3531 AN XY: 33569

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0366

Gnomad SAS AF: 0.0751

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.0906

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

GnomAD4 genome AF: 0.111 AC: 12328 AN: 111452 Hom.: 621 Cov.: 23 AF XY: 0.105 AC XY: 3531 AN XY: 33632

Gnomad4 AFR AF: 0.0393

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.0364

Gnomad4 SAS AF: 0.0753

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.0894

Alfa AF: 0.138 Hom.: 811

Bravo AF: 0.0981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.3
Dann	Benign	0.41

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: rs5924752; hg19: chrX-151817969;