Variant chrX-151954786-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004961.4(GABRE):c.1436G>A(p.Arg479His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,209,352 control chromosomes in the GnomAD database, including 1 homozygotes. There are 9 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 1 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000023 ( 0 hom. 9 hem. )

Consequence

GABRE
NM_004961.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRE	NM_004961.4 linkuse as main transcript	c.1436G>A	p.Arg479His	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.1436G>A	p.Arg479His	missense_variant	9/9	1	NM_004961.4	ENSP00000359353	P1	P78334-1
GABRE	ENST00000486255.1 linkuse as main transcript	n.4515G>A		non_coding_transcript_exon_variant	3/3	1
GABRE	ENST00000483564.5 linkuse as main transcript	n.1086G>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

112143

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34305

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000563

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000547

AC:

AN:

182938

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67438

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000228

AC:

AN:

1097209

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

362597

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000331

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000143

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000268

AC:

AN:

112143

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34305

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000563

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00000529

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2024

The c.1436G>A (p.R479H) alteration is located in exon 9 (coding exon 9) of the GABRE gene. This alteration results from a G to A substitution at nucleotide position 1436, causing the arginine (R) at amino acid position 479 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.80

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.56

MetaSVM

Uncertain

0.46

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.64

D;D

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.64

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.050

Polyphen

1.0

Vest4

0.13

MVP

0.90

MPC

0.41

ClinPred

0.99

GERP RS

4.8

Varity_R

0.26

gMVP

0.41

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