Variant rs28408173 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000378585.7(GABRD):c.816C>T(p.Ser272=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,569,906 control chromosomes in the GnomAD database, including 20,692 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1800 hom., cov: 34)

Exomes 𝑓: 0.15 ( 18892 hom. )

Consequence

GABRD
ENST00000378585.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.476

Variant links:

Genes affected

GABRD (HGNC:4084): (gamma-aminobutyric acid type A receptor subunit delta) Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. The GABA-A receptor is generally pentameric and there are five types of subunits: alpha, beta, gamma, delta, and rho. This gene encodes the delta subunit. Mutations in this gene have been associated with susceptibility to generalized epilepsy with febrile seizures, type 5. Alternatively spliced transcript variants have been described for this gene, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

GABRD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.3176806E-5).

BP6

Variant 1-2029235-C-T is Benign according to our data. Variant chr1-2029235-C-T is described in ClinVar as [Benign]. Clinvar id is 256825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-2029235-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.476 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GABRD	NM_000815.5 linkuse as main transcript	c.816C>T	p.Ser272=	synonymous_variant	7/9	ENST00000378585.7	NP_000806.2
GABRD	XM_017000936.2 linkuse as main transcript	c.1521C>T	p.Ser507=	synonymous_variant	6/8		XP_016856425.1
GABRD	XM_011541194.4 linkuse as main transcript	c.855C>T	p.Ser285=	synonymous_variant	7/9		XP_011539496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRD	ENST00000378585.7 linkuse as main transcript	c.816C>T	p.Ser272=	synonymous_variant	7/9	1	NM_000815.5	ENSP00000367848	P1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19216

AN:

152184

Hom.:

1790

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.147

GnomAD3 exomes

AF:

0.192

AC:

35320

AN:

184166

Hom.:

4375

AF XY:

0.195

AC XY:

19180

AN XY:

98252

show subpopulations

Gnomad AFR exome

AF:

0.0319

Gnomad AMR exome

AF:

0.238

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.472

Gnomad SAS exome

AF:

0.254

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.169

GnomAD4 exome

AF:

0.152

AC:

215491

AN:

1417604

Hom.:

18892

Cov.:

AF XY:

0.154

AC XY:

108357

AN XY:

701504

show subpopulations

Gnomad4 AFR exome

AF:

0.0302

Gnomad4 AMR exome

AF:

0.229

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.399

Gnomad4 SAS exome

AF:

0.248

Gnomad4 FIN exome

AF:

0.174

Gnomad4 NFE exome

AF:

0.137

Gnomad4 OTH exome

AF:

0.157

GnomAD4 genome

AF:

0.126

AC:

19243

AN:

152302

Hom.:

1800

Cov.:

AF XY:

0.132

AC XY:

9853

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0315

Gnomad4 AMR

AF:

0.159

Gnomad4 ASJ

AF:

0.117

Gnomad4 EAS

AF:

0.432

Gnomad4 SAS

AF:

0.267

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.155

Alfa

AF:

0.124

Hom.:

640

Bravo

AF:

0.124

TwinsUK

AF:

0.124

AC:

461

ALSPAC

AF:

0.138

AC:

531

ESP6500AA

AF:

0.0322

AC:

141

ESP6500EA

AF:

0.131

AC:

1123

ExAC

AF:

0.157

AC:

18364

Asia WGS

AF:

0.328

AC:

1140

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 27, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Idiopathic generalized epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

2.2

DANN

Benign

0.72

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.24

MetaRNN

Benign

0.000043

MutationTaster

Benign

3.6e-13

GERP RS

-3.4

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