rs2266858

Variant names:

• chrX-151973503-T-A
• rs2266858
• NM_004961.4:c.56+1067A>T

Your query was ambiguous. Multiple possible variants found:

• chrX-151973503-T-A
• chrX-151973503-T-C
• chrX-151973503-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004961.4(GABRE):​c.56+1067A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 109,868 control chromosomes in the GnomAD database, including 7,201 homozygotes. There are 13,287 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 0.42 (7201 hom., 13287 hem., cov: 22)
• Consequence: GABRE NM_004961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.535 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRE	NM_004961.4	MANE Select	c.56+1067A>T		intron	N/A	NP_004952.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRE	ENST00000370328.4	TSL:1 MANE Select	c.56+1067A>T		intron	N/A	ENSP00000359353.3	P78334-1
	GABRE	ENST00000417300.1	TSL:2	n.56+1067A>T		intron	N/A	ENSP00000397335.1	F2Z2H5
	GABRE	ENST00000441219.5	TSL:2	n.56+1067A>T		intron	N/A	ENSP00000389384.1	F2Z2H5

Frequencies

GnomAD3 genomes AF: 0.423 AC: 46400 AN: 109818 Hom.: 7198 Cov.: 22

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.423 AC: 46422 AN: 109868 Hom.: 7201 Cov.: 22 AF XY: 0.413 AC XY: 13287 AN XY: 32192

African (AFR) AF: 0.371 AC: 11150 AN: 30092

American (AMR) AF: 0.547 AC: 5666 AN: 10363

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 830 AN: 2625

East Asian (EAS) AF: 0.494 AC: 1691 AN: 3420

South Asian (SAS) AF: 0.375 AC: 958 AN: 2552

European-Finnish (FIN) AF: 0.349 AC: 2032 AN: 5815

Middle Eastern (MID) AF: 0.449 AC: 96 AN: 214

European-Non Finnish (NFE) AF: 0.438 AC: 23034 AN: 52633

Other (OTH) AF: 0.439 AC: 650 AN: 1482

Alfa AF: 0.430 Hom.: 2908

Bravo AF: 0.441

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.57
PhyloP100		-0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=98/2	polymorphism (auto)

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: rs2266858; hg19: chrX-151141975;