rs5970170

Positions:

• chrX-151953776-T-C

Variant summary

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

The NM_004961.4(GABRE):​c.*925A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 110,826 control chromosomes in the GnomAD database, including 709 homozygotes. There are 4,171 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 (709 hom., 4167 hem., cov: 23)
  • Exomes 𝑓: 0.21 (0 hom. 4 hem.)
• Consequence: GABRE NM_004961.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.595

Genes affected

GABRE (HGNC:4085): (gamma-aminobutyric acid type A receptor subunit epsilon) The product of this gene belongs to the ligand-gated ionic channel (TC 1.A.9) family. It encodes the gamma-aminobutyric acid (GABA) A receptor which is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes an epsilon subunit. It is mapped to chromosome Xq28 in a cluster comprised of genes encoding alpha 3, beta 4 and theta subunits of the same receptor. Alternatively spliced transcript variants have been identified, but only one is thought to encode a protein. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRE	NM_004961.4	c.*925A>G		3_prime_UTR_variant	9/9	ENST00000370328.4	NP_004952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRE	ENST00000370328.4	c.*925A>G		3_prime_UTR_variant	9/9	1	NM_004961.4	ENSP00000359353	P1
GABRE	ENST00000486255.1	n.5525A>G		non_coding_transcript_exon_variant	3/3	1
GABRE	ENST00000483564.5	n.2096A>G		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 14361 AN: 110745 Hom.: 710 Cov.: 23 AF XY: 0.126 AC XY: 4157 AN XY: 33039

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0886

Gnomad ASJ AF: 0.0759

Gnomad EAS AF: 0.00765

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0909

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.214 AC: 6 AN: 28 Hom.: 0 Cov.: 0 AF XY: 0.222 AC XY: 4 AN XY: 18

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.130 AC: 14370 AN: 110798 Hom.: 709 Cov.: 23 AF XY: 0.126 AC XY: 4167 AN XY: 33102

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0884

Gnomad4 ASJ AF: 0.0759

Gnomad4 EAS AF: 0.00767

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.132

Alfa AF: 0.127 Hom.: 4715

Bravo AF: 0.126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.47
DANN	Benign	0.55

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: rs5970170; hg19: chrX-151122248;