rs1417975898

Variant names:

• chrX-151955051-G-A
• rs1417975898
• NM_004961.4:c.1171C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-151955051-G-A
• chrX-151955051-G-C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_004961.4(GABRE):​c.1171C>T​(p.Arg391Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,088,772 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R391H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000028 (0 hom. 2 hem.)
• Consequence: GABRE NM_004961.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.256
• Publications: 1 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3077577).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

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.1171C>T	p.Arg391Cys	missense	Exon 9 of 9	NP_004952.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRE	ENST00000370328.4	TSL:1 MANE Select	c.1171C>T	p.Arg391Cys	missense	Exon 9 of 9	ENSP00000359353.3	P78334-1
	GABRE	ENST00000486255.1	TSL:1	n.4250C>T		non_coding_transcript_exon	Exon 3 of 3
	GABRE	ENST00000483564.5	TSL:3	n.821C>T		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000122 AC: 2 AN: 163320 AF XY: 0.0000197

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000154

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000276 AC: 3 AN: 1088772 Hom.: 0 Cov.: 32 AF XY: 0.00000563 AC XY: 2 AN XY: 355402

African (AFR) AF: 0.00 AC: 0 AN: 26286

American (AMR) AF: 0.00 AC: 0 AN: 34433

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18996

East Asian (EAS) AF: 0.0000668 AC: 2 AN: 29919

South Asian (SAS) AF: 0.0000191 AC: 1 AN: 52299

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4114

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 837131

Other (OTH) AF: 0.00 AC: 0 AN: 45694

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.26
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.26
Sift	Benign	0.048	D
Sift4G	Uncertain	0.042	D
Polyphen		1.0	D
Vest4		0.11
MutPred		0.54		Loss of methylation at R391 (P = 0.0384)
MVP		0.88
MPC		0.079
ClinPred		0.29	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.096
gMVP		0.27
Mutation Taster		=94/6	polymorphism

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: rs1417975898; hg19: chrX-151123523;