X-151973060-T-G

Variant names:

• chrX-151973060-T-G
• rs2266856
• NM_004961.4:c.56+1510A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004961.4(GABRE):​c.56+1510A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 109,070 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 0.000046 (0 hom., 1 hem., cov: 21)
• Consequence: GABRE NM_004961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.987
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.56+1510A>C		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.56+1510A>C		intron	N/A	ENSP00000359353.3	P78334-1
	GABRE	ENST00000417300.1	TSL:2	n.56+1510A>C		intron	N/A	ENSP00000397335.1	F2Z2H5
	GABRE	ENST00000441219.5	TSL:2	n.56+1510A>C		intron	N/A	ENSP00000389384.1	F2Z2H5

Frequencies

GnomAD3 genomes AF: 0.0000458 AC: 5 AN: 109070 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000953

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000458 AC: 5 AN: 109070 Hom.: 0 Cov.: 21 AF XY: 0.0000319 AC XY: 1 AN XY: 31352

African (AFR) AF: 0.00 AC: 0 AN: 30001

American (AMR) AF: 0.00 AC: 0 AN: 10253

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2617

East Asian (EAS) AF: 0.00 AC: 0 AN: 3400

South Asian (SAS) AF: 0.00 AC: 0 AN: 2430

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5519

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 232

European-Non Finnish (NFE) AF: 0.0000953 AC: 5 AN: 52482

Other (OTH) AF: 0.00 AC: 0 AN: 1458

Alfa AF: 0.00 Hom.: 20946

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.7
DANN	Benign	0.58
PhyloP100		0.99

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: rs2266856; hg19: chrX-151141532;