rs1061418

Variant names:

• chrX-151954508-G-A
• rs1061418
• ENST00000486255.1:n.4793C>T

Variant summary

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

The ENST00000486255.1(GABRE):​n.4793C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0997 in 414,123 control chromosomes in the GnomAD database, including 1,936 homozygotes. There are 12,277 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 0.085 (429 hom., 2751 hem., cov: 22)
  • Exomes 𝑓: 0.11 (1507 hom. 9526 hem.)
• Consequence: GABRE ENST00000486255.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 3 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 (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRE	NM_004961.4	c.*193C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000370328.4	NP_004952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRE	ENST00000486255.1	n.4793C>T		non_coding_transcript_exon_variant	Exon 3 of 3	1
GABRE	ENST00000370328.4	c.*193C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_004961.4	ENSP00000359353.3
GABRE	ENST00000483564.5	n.1364C>T		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.0853 AC: 9499 AN: 111377 Hom.: 429 Cov.: 22

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0411

Gnomad ASJ AF: 0.0531

Gnomad EAS AF: 0.00113

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0258

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.0666

GnomAD4 exome AF: 0.105 AC: 31812 AN: 302692 Hom.: 1507 Cov.: 2 AF XY: 0.0992 AC XY: 9526 AN XY: 95996

African (AFR) AF: 0.0174 AC: 156 AN: 8985

American (AMR) AF: 0.0328 AC: 367 AN: 11174

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 498 AN: 9370

East Asian (EAS) AF: 0.0000459 AC: 1 AN: 21780

South Asian (SAS) AF: 0.0166 AC: 332 AN: 19951

European-Finnish (FIN) AF: 0.164 AC: 4515 AN: 27570

Middle Eastern (MID) AF: 0.0267 AC: 35 AN: 1311

European-Non Finnish (NFE) AF: 0.131 AC: 24195 AN: 184155

Other (OTH) AF: 0.0931 AC: 1713 AN: 18396

GnomAD4 genome AF: 0.0852 AC: 9495 AN: 111431 Hom.: 429 Cov.: 22 AF XY: 0.0818 AC XY: 2751 AN XY: 33615

African (AFR) AF: 0.0171 AC: 525 AN: 30738

American (AMR) AF: 0.0409 AC: 432 AN: 10555

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 140 AN: 2639

East Asian (EAS) AF: 0.00114 AC: 4 AN: 3523

South Asian (SAS) AF: 0.0138 AC: 36 AN: 2615

European-Finnish (FIN) AF: 0.168 AC: 1006 AN: 5975

Middle Eastern (MID) AF: 0.0280 AC: 6 AN: 214

European-Non Finnish (NFE) AF: 0.135 AC: 7171 AN: 52975

Other (OTH) AF: 0.0657 AC: 100 AN: 1522

Alfa AF: 0.109 Hom.: 1883

Bravo AF: 0.0729

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.33
PhyloP100		-0.18
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: rs1061418; hg19: chrX-151122980;