NM_004961.4:c.56+245G>A

Variant names:

• chrX-151974325-C-T
• rs5925077
• NM_004961.4:c.56+245G>A

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+245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 110,721 control chromosomes in the GnomAD database, including 4,631 homozygotes. There are 10,864 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 0.34 (4631 hom., 10864 hem., cov: 22)
• Consequence: GABRE NM_004961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRE	NM_004961.4	c.56+245G>A		intron_variant	Intron 1 of 8	ENST00000370328.4	NP_004952.2
GABRE	XM_047441959.1	c.-3469G>A		5_prime_UTR_variant	Exon 1 of 9		XP_047297915.1
GABRE	XM_047441960.1	c.-3917G>A		5_prime_UTR_variant	Exon 1 of 9		XP_047297916.1
GABRE	XM_024452360.2	c.-462+245G>A		intron_variant	Intron 1 of 9		XP_024308128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRE	ENST00000370328.4	c.56+245G>A		intron_variant	Intron 1 of 8	1	NM_004961.4	ENSP00000359353.3
GABRE	ENST00000417300.1	n.56+245G>A		intron_variant	Intron 1 of 2	2		ENSP00000397335.1
GABRE	ENST00000441219.5	n.56+245G>A		intron_variant	Intron 1 of 7	2		ENSP00000389384.1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 37589 AN: 110676 Hom.: 4628 Cov.: 22

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.340 AC: 37607 AN: 110721 Hom.: 4631 Cov.: 22 AF XY: 0.329 AC XY: 10864 AN XY: 33013

African (AFR) AF: 0.338 AC: 10319 AN: 30505

American (AMR) AF: 0.385 AC: 4081 AN: 10590

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 912 AN: 2637

East Asian (EAS) AF: 0.344 AC: 1163 AN: 3379

South Asian (SAS) AF: 0.311 AC: 816 AN: 2622

European-Finnish (FIN) AF: 0.289 AC: 1716 AN: 5940

Middle Eastern (MID) AF: 0.332 AC: 70 AN: 211

European-Non Finnish (NFE) AF: 0.336 AC: 17722 AN: 52681

Other (OTH) AF: 0.351 AC: 525 AN: 1495

Alfa AF: 0.336 Hom.: 30902

Bravo AF: 0.351

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.73
PhyloP100		-0.21
PromoterAI		0.037	Neutral
Mutation Taster		=100/0	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: rs5925077; hg19: chrX-151142797;