rs2256882

chrX-151961350-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_004961.4(GABRE):c.579C>T(p.Ala193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,198,075 control chromosomes in the GnomAD database, including 15,003 homozygotes. There are 59,479 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 0.26 (4284 hom., 8005 hem., cov: 22)
  • Exomes 𝑓: 0.15 (10719 hom. 51474 hem.)
• Consequence: GABRE NM_004961.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=-0.475 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRE	NM_004961.4	c.579C>T	p.Ala193=	synonymous_variant	5/9	ENST00000370328.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRE	ENST00000370328.4	c.579C>T	p.Ala193=	synonymous_variant	5/9	1	NM_004961.4	P1
GABRE	ENST00000474932.1	n.305C>T		non_coding_transcript_exon_variant	3/3	5
GABRE	ENST00000441219.5	c.*609+1073C>T		intron_variant, NMD_transcript_variant		2
GABRE	ENST00000476016.1	n.171+1073C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.261 AC: 28688 AN: 110061 Hom.: 4287 Cov.: 22 AF XY: 0.246 AC XY: 7962 AN XY: 32369

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.228

GnomAD3 exomes AF: 0.185 AC: 33695 AN: 182607 Hom.: 3176 AF XY: 0.169 AC XY: 11323 AN XY: 67139

Gnomad AFR exome AF: 0.583

Gnomad AMR exome AF: 0.138

Gnomad ASJ exome AF: 0.150

Gnomad EAS exome AF: 0.337

Gnomad SAS exome AF: 0.165

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.147 AC: 159831 AN: 1087956 Hom.: 10719 Cov.: 27 AF XY: 0.145 AC XY: 51474 AN XY: 354802

Gnomad4 AFR exome AF: 0.586

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.261 AC: 28728 AN: 110119 Hom.: 4284 Cov.: 22 AF XY: 0.247 AC XY: 8005 AN XY: 32437

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.230

Alfa AF: 0.154 Hom.: 9096

Bravo AF: 0.280

EpiCase AF: 0.120

EpiControl AF: 0.124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	7.4
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2256882; hg19: chrX-151129822; COSMIC: COSV64819186; COSMIC: COSV64819186;