Variant rs41315330 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000815.5(GABRD):c.1002C>T(p.Asn334Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0025 in 1,613,494 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 9 hom. )

Consequence

GABRD
NM_000815.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.781

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:

GABRD (HGNC:):

GABRD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004554063).

BP6

Variant 1-2029705-C-T is Benign according to our data. Variant chr1-2029705-C-T is described in ClinVar as [Benign]. Clinvar id is 460002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-2029705-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.781 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRD	NM_000815.5 linkuse as main transcript	c.1002C>T	p.Asn334Asn	synonymous_variant	8/9	ENST00000378585.7	NP_000806.2	O14764A8K496
GABRD	XM_017000936.2 linkuse as main transcript	c.1707C>T	p.Asn569Asn	synonymous_variant	7/8		XP_016856425.1
GABRD	XM_011541194.4 linkuse as main transcript	c.1041C>T	p.Asn347Asn	synonymous_variant	8/9		XP_011539496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRD	ENST00000378585.7 linkuse as main transcript	c.1002C>T	p.Asn334Asn	synonymous_variant	8/9	1	NM_000815.5	ENSP00000367848.4		O14764

Frequencies

GnomAD3 genomes

AF:

0.00185

AC:

282

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00278

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00192

AC:

482

AN:

250568

Hom.:

AF XY:

0.00190

AC XY:

258

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.000681

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00329

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.00256

AC:

3745

AN:

1461144

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

1805

AN XY:

726870

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.000626

Gnomad4 NFE exome

AF:

0.00310

Gnomad4 OTH exome

AF:

0.00217

GnomAD4 genome

AF:

0.00185

AC:

282

AN:

152350

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

126

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00278

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00221

Hom.:

Bravo

AF:

0.00215

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00218

AC:

265

EpiCase

AF:

0.00262

EpiControl

AF:

0.00362

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.19

DANN

Benign

0.52

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0046

GERP RS

-8.0

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