rs2266858

chrX-151973503-T-AchrX-151973503-T-CchrX-151973503-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRE	NM_004961.4	c.56+1067A>T		intron_variant		ENST00000370328.4
GABRE	XM_047441959.1	c.-2647A>T		5_prime_UTR_variant	1/9
GABRE	XM_047441960.1	c.-3095A>T		5_prime_UTR_variant	1/9
GABRE	XM_024452360.2	c.-462+1067A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRE	ENST00000370328.4	c.56+1067A>T		intron_variant		1	NM_004961.4	P1
GABRE	ENST00000417300.1	c.56+1067A>T		intron_variant, NMD_transcript_variant		2
GABRE	ENST00000441219.5	c.56+1067A>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.423 AC: 46400 AN: 109818 Hom.: 7198 Cov.: 22 AF XY: 0.413 AC XY: 13261 AN XY: 32132

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

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.439

Alfa AF: 0.430 Hom.: 2908

Bravo AF: 0.441

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	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2266858; hg19: chrX-151141975;