rs2256882

Variant names:

• chrX-151961350-G-A
• rs2256882
• NM_004961.4:c.579C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_004961.4(GABRE):​c.579C>T​(p.Ala193Ala) 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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004961.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRE	NM_004961.4	MANE Select	c.579C>T	p.Ala193Ala	synonymous	Exon 5 of 9	NP_004952.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRE	ENST00000370328.4	TSL:1 MANE Select	c.579C>T	p.Ala193Ala	synonymous	Exon 5 of 9	ENSP00000359353.3
	GABRE	ENST00000474932.1	TSL:5	n.305C>T		non_coding_transcript_exon	Exon 3 of 3
	GABRE	ENST00000441219.5	TSL:2	n.*609+1073C>T		intron	N/A	ENSP00000389384.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 28688 AN: 110061 Hom.: 4287 Cov.: 22

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

GnomAD2 exomes AF: 0.185 AC: 33695 AN: 182607 AF XY: 0.169

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 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

African (AFR) AF: 0.586 AC: 15327 AN: 26157

American (AMR) AF: 0.140 AC: 4923 AN: 35139

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 2863 AN: 19293

East Asian (EAS) AF: 0.346 AC: 10439 AN: 30152

South Asian (SAS) AF: 0.165 AC: 8886 AN: 53874

European-Finnish (FIN) AF: 0.170 AC: 6891 AN: 40502

Middle Eastern (MID) AF: 0.114 AC: 469 AN: 4109

European-Non Finnish (NFE) AF: 0.123 AC: 102401 AN: 832997

Other (OTH) AF: 0.167 AC: 7632 AN: 45733

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

African (AFR) AF: 0.573 AC: 17259 AN: 30104

American (AMR) AF: 0.159 AC: 1654 AN: 10407

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 357 AN: 2627

East Asian (EAS) AF: 0.329 AC: 1129 AN: 3430

South Asian (SAS) AF: 0.170 AC: 435 AN: 2553

European-Finnish (FIN) AF: 0.153 AC: 896 AN: 5869

Middle Eastern (MID) AF: 0.117 AC: 25 AN: 214

European-Non Finnish (NFE) AF: 0.124 AC: 6551 AN: 52750

Other (OTH) AF: 0.230 AC: 342 AN: 1485

Alfa AF: 0.173 Hom.: 14731

Bravo AF: 0.280

EpiCase AF: 0.120

EpiControl AF: 0.124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.4
DANN	Benign	0.80
PhyloP100		-0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2256882; hg19: chrX-151129822; COSMIC: COSV64819186; COSMIC: COSV64819186;