Variant X-151954807-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_004961.4(GABRE):c.1415G>A(p.Arg472His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,210,161 control chromosomes in the GnomAD database, including 9 homozygotes. There are 1,080 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., 46 hem., cov: 23)

Exomes 𝑓: 0.0029 ( 8 hom. 1034 hem. )

Consequence

GABRE
NM_004961.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.51

Variant links:

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]

GABRE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011199564).

BP6

Variant X-151954807-C-T is Benign according to our data. Variant chrX-151954807-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3043062.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 46 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRE	NM_004961.4 linkuse as main transcript	c.1415G>A	p.Arg472His	missense_variant	9/9	ENST00000370328.4	NP_004952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRE	ENST00000370328.4 linkuse as main transcript	c.1415G>A	p.Arg472His	missense_variant	9/9	1	NM_004961.4	ENSP00000359353	P1	P78334-1
GABRE	ENST00000486255.1 linkuse as main transcript	n.4494G>A		non_coding_transcript_exon_variant	3/3	1
GABRE	ENST00000483564.5 linkuse as main transcript	n.1065G>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

158

AN:

112307

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

AN XY:

34455

show subpopulations

Gnomad AFR

AF:

0.000259

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000375

Gnomad ASJ

AF:

0.00452

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000741

Gnomad FIN

AF:

0.000812

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00235

Gnomad OTH

AF:

0.00133

GnomAD3 exomes

AF:

0.00185

AC:

339

AN:

182948

Hom.:

AF XY:

0.00197

AC XY:

133

AN XY:

67486

show subpopulations

Gnomad AFR exome

AF:

0.000382

Gnomad AMR exome

AF:

0.000621

Gnomad ASJ exome

AF:

0.00335

Gnomad EAS exome

AF:

0.000362

Gnomad SAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.00276

Gnomad NFE exome

AF:

0.00250

Gnomad OTH exome

AF:

0.00243

GnomAD4 exome

AF:

0.00285

AC:

3129

AN:

1097801

Hom.:

Cov.:

AF XY:

0.00285

AC XY:

1034

AN XY:

363159

show subpopulations

Gnomad4 AFR exome

AF:

0.000265

Gnomad4 AMR exome

AF:

0.000682

Gnomad4 ASJ exome

AF:

0.00325

Gnomad4 EAS exome

AF:

0.000199

Gnomad4 SAS exome

AF:

0.00155

Gnomad4 FIN exome

AF:

0.00274

Gnomad4 NFE exome

AF:

0.00321

Gnomad4 OTH exome

AF:

0.00282

GnomAD4 genome

AF:

0.00141

AC:

158

AN:

112360

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

34518

show subpopulations

Gnomad4 AFR

AF:

0.000258

Gnomad4 AMR

AF:

0.000374

Gnomad4 ASJ

AF:

0.00452

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000743

Gnomad4 FIN

AF:

0.000812

Gnomad4 NFE

AF:

0.00235

Gnomad4 OTH

AF:

0.00132

Alfa

AF:

0.00238

Hom.:

101

Bravo

AF:

0.00120

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00223

AC:

ExAC

AF:

0.00189

AC:

229

EpiCase

AF:

0.00245

EpiControl

AF:

0.00196

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GABRE-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 26, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.35

Sift

Benign

0.039

Sift4G

Uncertain

0.011

Polyphen

0.39

Vest4

0.040

MVP

0.92

MPC

0.33

ClinPred

0.050

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.34

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over