chrX-152649506-G-C

Variant names:

• chrX-152649506-G-C
• rs5924752
• NM_018558.4:c.610+173G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GABRQ	NM_018558.4	c.610+173G>C		intron_variant	Intron 5 of 8	ENST00000598523.3	NP_061028.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRQ	ENST00000598523.3	c.610+173G>C		intron_variant	Intron 5 of 8	1	NM_018558.4	ENSP00000469332.1
MAGEA3-DT	ENST00000671457.1	n.130-9712C>G		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.111 AC: 12333 AN: 111399 Hom.: 622 Cov.: 23

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

African (AFR) AF: 0.0393 AC: 1208 AN: 30706

American (AMR) AF: 0.0628 AC: 662 AN: 10544

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 275 AN: 2650

East Asian (EAS) AF: 0.0364 AC: 129 AN: 3543

South Asian (SAS) AF: 0.0753 AC: 197 AN: 2616

European-Finnish (FIN) AF: 0.186 AC: 1107 AN: 5947

Middle Eastern (MID) AF: 0.0968 AC: 21 AN: 217

European-Non Finnish (NFE) AF: 0.159 AC: 8441 AN: 53017

Other (OTH) AF: 0.0894 AC: 137 AN: 1532

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
PhyloP100		0.34

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: rs5924752; hg19: chrX-151817969;