rs2266856

chrX-151973060-T-CchrX-151973060-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004961.4(GABRE):c.56+1510A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.58 (15293 hom., 18265 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: GABRE NM_004961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.987

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS2: High Homozygotes in GnomAd at 15293 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRE	NM_004961.4	c.56+1510A>G		intron_variant		ENST00000370328.4
GABRE	XM_047441959.1	c.-2204A>G		5_prime_UTR_variant	1/9
GABRE	XM_047441960.1	c.-2652A>G		5_prime_UTR_variant	1/9
GABRE	XM_024452360.2	c.-462+1510A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRE	ENST00000370328.4	c.56+1510A>G		intron_variant		1	NM_004961.4	P1
GABRE	ENST00000417300.1	c.56+1510A>G		intron_variant, NMD_transcript_variant		2
GABRE	ENST00000441219.5	c.56+1510A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.583 AC: 63519 AN: 108979 Hom.: 15293 Cov.: 21 AF XY: 0.583 AC XY: 18241 AN XY: 31295

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.594

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.583 AC: 63536 AN: 109029 Hom.: 15293 Cov.: 21 AF XY: 0.583 AC XY: 18265 AN XY: 31355

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.740

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.726

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.596

Alfa AF: 0.661 Hom.: 12974

Bravo AF: 0.563

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.9
Dann	Benign	0.63

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: rs2266856; hg19: chrX-151141532;