dbSNP rs2256882: GABRE:p.Ala193Ala (chrX-151961350-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_004961.4(GABRE):c.579C>T(p.Ala193Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,198,075 control chromosomes in the GnomAD database, including 15,003 homozygotes. There are 59,479 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 0.26 ( 4284 hom., 8005 hem., cov: 22)

Exomes 𝑓: 0.15 ( 10719 hom. 51474 hem. )

Consequence

GABRE
NM_004961.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.475

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 Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP7

Synonymous conserved (PhyloP=-0.475 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRE	NM_004961.4 link	c.579C>T	p.Ala193Ala	synonymous_variant	Exon 5 of 9	ENST00000370328.4	NP_004952.2	P78334-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GABRE	ENST00000370328.4 link	c.579C>T	p.Ala193Ala	synonymous_variant	Exon 5 of 9	1	NM_004961.4	ENSP00000359353.3	P78334-1
GABRE	ENST00000474932.1 link	n.305C>T		non_coding_transcript_exon_variant	Exon 3 of 3	5
GABRE	ENST00000441219.5 link	n.*609+1073C>T		intron_variant	Intron 5 of 7	2		ENSP00000389384.1	F2Z2H5
GABRE	ENST00000476016.1 link	n.171+1073C>T		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

28688

AN:

110061

Hom.:

4287

Cov.:

AF XY:

0.246

AC XY:

7962

AN XY:

32369

show subpopulations

Gnomad AFR

AF:

0.573

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.228

GnomAD3 exomes

AF:

0.185

AC:

33695

AN:

182607

Hom.:

3176

AF XY:

0.169

AC XY:

11323

AN XY:

67139

show subpopulations

Gnomad AFR exome

AF:

0.583

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.337

Gnomad SAS exome

AF:

0.165

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.123

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.147

AC:

159831

AN:

1087956

Hom.:

10719

Cov.:

AF XY:

0.145

AC XY:

51474

AN XY:

354802

show subpopulations

Gnomad4 AFR exome

AF:

0.586

Gnomad4 AMR exome

AF:

0.140

Gnomad4 ASJ exome

AF:

0.148

Gnomad4 EAS exome

AF:

0.346

Gnomad4 SAS exome

AF:

0.165

Gnomad4 FIN exome

AF:

0.170

Gnomad4 NFE exome

AF:

0.123

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.261

AC:

28728

AN:

110119

Hom.:

4284

Cov.:

AF XY:

0.247

AC XY:

8005

AN XY:

32437

show subpopulations

Gnomad4 AFR

AF:

0.573

Gnomad4 AMR

AF:

0.159

Gnomad4 ASJ

AF:

0.136

Gnomad4 EAS

AF:

0.329

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.124

Gnomad4 OTH

AF:

0.230

Alfa

AF:

0.154

Hom.:

9096

Bravo

AF:

0.280

EpiCase

AF:

0.120

EpiControl

AF:

0.124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

7.4

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over