rs1003794

Variant names:

• chrX-151966832-G-C
• rs1003794
• NM_004961.4:c.342+2837C>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.342+2837C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 111,197 control chromosomes in the GnomAD database, including 4,901 homozygotes. There are 11,121 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 0.35 (4901 hom., 11121 hem., cov: 24)
• Consequence: GABRE NM_004961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 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.342+2837C>G		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.342+2837C>G		intron	N/A	ENSP00000359353.3	P78334-1
	GABRE	ENST00000441219.5	TSL:2	n.*388+2837C>G		intron	N/A	ENSP00000389384.1	F2Z2H5
	GABRE	ENST00000474932.1	TSL:5	n.68+2837C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.347 AC: 38536 AN: 111140 Hom.: 4907 Cov.: 24

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.347 AC: 38540 AN: 111197 Hom.: 4901 Cov.: 24 AF XY: 0.333 AC XY: 11121 AN XY: 33419

African (AFR) AF: 0.346 AC: 10561 AN: 30541

American (AMR) AF: 0.271 AC: 2859 AN: 10557

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1060 AN: 2641

East Asian (EAS) AF: 0.437 AC: 1527 AN: 3497

South Asian (SAS) AF: 0.286 AC: 754 AN: 2634

European-Finnish (FIN) AF: 0.362 AC: 2144 AN: 5919

Middle Eastern (MID) AF: 0.263 AC: 57 AN: 217

European-Non Finnish (NFE) AF: 0.357 AC: 18907 AN: 52995

Other (OTH) AF: 0.343 AC: 521 AN: 1520

Alfa AF: 0.353 Hom.: 2299

Bravo AF: 0.345

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.59
PhyloP100		1.5
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: rs1003794; hg19: chrX-151135304;