Variant chrX-151969707-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_004961.4(GABRE):c.304T>G(p.Ser102Ala) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.64 ( 16408 hom., 20676 hem., cov: 22)

Exomes 𝑓: 0.70 ( 178081 hom. 253983 hem. )

Failed GnomAD Quality Control

Consequence

GABRE
NM_004961.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.11

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0047327E-4).

BP6

Variant X-151969707-A-C is Benign according to our data. Variant chrX-151969707-A-C is described in ClinVar as [Benign]. Clinvar id is 1280403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRE	NM_004961.4 link	c.304T>G	p.Ser102Ala	missense_variant	3/9	ENST00000370328.4	NP_004952.2	P78334-1
GABRE	XM_024452360.2 link	c.-36T>G		5_prime_UTR_variant	4/10		XP_024308128.1
GABRE	XM_047441959.1 link	c.-36T>G		5_prime_UTR_variant	3/9		XP_047297915.1
GABRE	XM_047441960.1 link	c.-36T>G		5_prime_UTR_variant	2/9		XP_047297916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRE	ENST00000370328.4 link	c.304T>G	p.Ser102Ala	missense_variant	3/9	1	NM_004961.4	ENSP00000359353.3		P78334-1

Frequencies

GnomAD3 genomes

AF:

0.644

AC:

70536

AN:

109473

Hom.:

16409

Cov.:

AF XY:

0.650

AC XY:

20649

AN XY:

31775

show subpopulations

Gnomad AFR

AF:

0.497

Gnomad AMI

AF:

0.623

Gnomad AMR

AF:

0.683

Gnomad ASJ

AF:

0.598

Gnomad EAS

AF:

0.872

Gnomad SAS

AF:

0.804

Gnomad FIN

AF:

0.809

Gnomad MID

AF:

0.625

Gnomad NFE

AF:

0.684

Gnomad OTH

AF:

0.624

GnomAD3 exomes

AF:

0.716

AC:

130407

AN:

182165

Hom.:

29673

AF XY:

0.726

AC XY:

48429

AN XY:

66681

show subpopulations

Gnomad AFR exome

AF:

0.494

Gnomad AMR exome

AF:

0.747

Gnomad ASJ exome

AF:

0.610

Gnomad EAS exome

AF:

0.868

Gnomad SAS exome

AF:

0.818

Gnomad FIN exome

AF:

0.801

Gnomad NFE exome

AF:

0.685

Gnomad OTH exome

AF:

0.715

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.696

AC:

763144

AN:

1096589

Hom.:

178081

Cov.:

AF XY:

0.701

AC XY:

253983

AN XY:

362189

show subpopulations

Gnomad4 AFR exome

AF:

0.487

Gnomad4 AMR exome

AF:

0.748

Gnomad4 ASJ exome

AF:

0.612

Gnomad4 EAS exome

AF:

0.893

Gnomad4 SAS exome

AF:

0.817

Gnomad4 FIN exome

AF:

0.795

Gnomad4 NFE exome

AF:

0.683

Gnomad4 OTH exome

AF:

0.685

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.644

AC:

70564

AN:

109531

Hom.:

16408

Cov.:

AF XY:

0.649

AC XY:

20676

AN XY:

31843

show subpopulations

Gnomad4 AFR

AF:

0.497

Gnomad4 AMR

AF:

0.684

Gnomad4 ASJ

AF:

0.598

Gnomad4 EAS

AF:

0.871

Gnomad4 SAS

AF:

0.804

Gnomad4 FIN

AF:

0.809

Gnomad4 NFE

AF:

0.684

Gnomad4 OTH

AF:

0.627

Alfa

AF:

0.682

Hom.:

63764

Bravo

AF:

0.632

TwinsUK

AF:

0.677

AC:

2509

ALSPAC

AF:

0.694

AC:

2004

ESP6500AA

AF:

0.504

AC:

1933

ESP6500EA

AF:

0.670

AC:

4511

ExAC

AF:

0.716

AC:

86879

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 14, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.061

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.73

MetaRNN

Benign

0.00010

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.32

REVEL

Benign

0.21

Sift

Uncertain

0.017

Sift4G

Benign

0.16

Polyphen

0.78

Vest4

0.032

MPC

0.082

ClinPred

0.024

GERP RS

2.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

Varity_R

0.17

gMVP

0.27

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