Variant rs2376805 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000815.5(GABRD):c.69-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 1,568,616 control chromosomes in the GnomAD database, including 528,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 50323 hom., cov: 36)

Exomes 𝑓: 0.82 ( 477942 hom. )

Consequence

GABRD
NM_000815.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.221

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-2024923-G-A is Benign according to our data. Variant chr1-2024923-G-A is described in ClinVar as [Benign]. Clinvar id is 256824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-2024923-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.825 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.69-19G>A		intron_variant		ENST00000378585.7	NP_000806.2
GABRD	XM_017000936.2 linkuse as main transcript	c.755G>A	p.Arg252Gln	missense_variant	1/8		XP_016856425.1
GABRD	XM_011541194.4 linkuse as main transcript	c.108-19G>A		intron_variant			XP_011539496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRD	ENST00000378585.7 linkuse as main transcript	c.69-19G>A		intron_variant		1	NM_000815.5	ENSP00000367848	P1

Frequencies

GnomAD3 genomes

AF:

0.813

AC:

123660

AN:

152152

Hom.:

50293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.795

Gnomad AMI

AF:

0.934

Gnomad AMR

AF:

0.768

Gnomad ASJ

AF:

0.904

Gnomad EAS

AF:

0.719

Gnomad SAS

AF:

0.781

Gnomad FIN

AF:

0.847

Gnomad MID

AF:

0.892

Gnomad NFE

AF:

0.830

Gnomad OTH

AF:

0.827

GnomAD3 exomes

AF:

0.803

AC:

200186

AN:

249240

Hom.:

80725

AF XY:

0.807

AC XY:

108942

AN XY:

135064

show subpopulations

Gnomad AFR exome

AF:

0.794

Gnomad AMR exome

AF:

0.739

Gnomad ASJ exome

AF:

0.883

Gnomad EAS exome

AF:

0.717

Gnomad SAS exome

AF:

0.772

Gnomad FIN exome

AF:

0.841

Gnomad NFE exome

AF:

0.831

Gnomad OTH exome

AF:

0.824

GnomAD4 exome

AF:

0.821

AC:

1162309

AN:

1416348

Hom.:

477942

Cov.:

AF XY:

0.820

AC XY:

579931

AN XY:

707314

show subpopulations

Gnomad4 AFR exome

AF:

0.800

Gnomad4 AMR exome

AF:

0.744

Gnomad4 ASJ exome

AF:

0.887

Gnomad4 EAS exome

AF:

0.727

Gnomad4 SAS exome

AF:

0.770

Gnomad4 FIN exome

AF:

0.843

Gnomad4 NFE exome

AF:

0.829

Gnomad4 OTH exome

AF:

0.823

GnomAD4 genome

AF:

0.813

AC:

123740

AN:

152268

Hom.:

50323

Cov.:

AF XY:

0.811

AC XY:

60364

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.795

Gnomad4 AMR

AF:

0.767

Gnomad4 ASJ

AF:

0.904

Gnomad4 EAS

AF:

0.720

Gnomad4 SAS

AF:

0.780

Gnomad4 FIN

AF:

0.847

Gnomad4 NFE

AF:

0.830

Gnomad4 OTH

AF:

0.828

Alfa

AF:

0.829

Hom.:

9602

Bravo

AF:

0.808

Asia WGS

AF:

0.755

AC:

2631

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Epilepsy, idiopathic generalized, susceptibility to, 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

-0.88

CADD

Benign

1.1

DANN

Benign

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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