rs1061418

Positions:

• chrX-151954508-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004961.4(GABRE):​c.*193C>T variant causes a 3 prime UTR 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 NM_004961.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180

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=-0.9).
• 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/exons	MANE	UniProt
GABRE	NM_004961.4	c.*193C>T		3_prime_UTR_variant	9/9	ENST00000370328.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRE	ENST00000370328.4	c.*193C>T		3_prime_UTR_variant	9/9	1	NM_004961.4	P1
GABRE	ENST00000486255.1	n.4793C>T		non_coding_transcript_exon_variant	3/3	1
GABRE	ENST00000483564.5	n.1364C>T		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.0853 AC: 9499 AN: 111377 Hom.: 429 Cov.: 22 AF XY: 0.0820 AC XY: 2752 AN XY: 33551

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

Gnomad4 AFR exome AF: 0.0174

Gnomad4 AMR exome AF: 0.0328

Gnomad4 ASJ exome AF: 0.0531

Gnomad4 EAS exome AF: 0.0000459

Gnomad4 SAS exome AF: 0.0166

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.0931

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

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.0409

Gnomad4 ASJ AF: 0.0531

Gnomad4 EAS AF: 0.00114

Gnomad4 SAS AF: 0.0138

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.0657

Alfa AF: 0.111 Hom.: 1787

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

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: rs1061418; hg19: chrX-151122980;