Variant 1-2030027-C-T 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 NM_000815.5(GABRD):c.1104C>T(p.Ala368=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 1,612,650 control chromosomes in the GnomAD database, including 1,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 106 hom., cov: 33)

Exomes 𝑓: 0.032 ( 957 hom. )

Consequence

GABRD
NM_000815.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.34

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=0.0015837848).

BP6

Variant 1-2030027-C-T is Benign according to our data. Variant chr1-2030027-C-T is described in ClinVar as [Benign]. Clinvar id is 460004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-2030027-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.34 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 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.1104C>T	p.Ala368=	synonymous_variant	9/9	ENST00000378585.7	NP_000806.2
GABRD	XM_017000936.2 linkuse as main transcript	c.1809C>T	p.Ala603=	synonymous_variant	8/8		XP_016856425.1
GABRD	XM_011541194.4 linkuse as main transcript	c.1143C>T	p.Ala381=	synonymous_variant	9/9		XP_011539496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRD	ENST00000378585.7 linkuse as main transcript	c.1104C>T	p.Ala368=	synonymous_variant	9/9	1	NM_000815.5	ENSP00000367848	P1

Frequencies

GnomAD3 genomes

AF:

0.0288

AC:

4391

AN:

152246

Hom.:

106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00579

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0265

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.0364

Gnomad FIN

AF:

0.0631

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0290

Gnomad OTH

AF:

0.0392

GnomAD3 exomes

AF:

0.0396

AC:

9827

AN:

248252

Hom.:

290

AF XY:

0.0401

AC XY:

5409

AN XY:

134996

show subpopulations

Gnomad AFR exome

AF:

0.00576

Gnomad AMR exome

AF:

0.0238

Gnomad ASJ exome

AF:

0.0631

Gnomad EAS exome

AF:

0.125

Gnomad SAS exome

AF:

0.0347

Gnomad FIN exome

AF:

0.0644

Gnomad NFE exome

AF:

0.0295

Gnomad OTH exome

AF:

0.0429

GnomAD4 exome

AF:

0.0324

AC:

47277

AN:

1460286

Hom.:

957

Cov.:

AF XY:

0.0328

AC XY:

23798

AN XY:

726424

show subpopulations

Gnomad4 AFR exome

AF:

0.00526

Gnomad4 AMR exome

AF:

0.0236

Gnomad4 ASJ exome

AF:

0.0616

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.0335

Gnomad4 FIN exome

AF:

0.0632

Gnomad4 NFE exome

AF:

0.0285

Gnomad4 OTH exome

AF:

0.0373

GnomAD4 genome

AF:

0.0288

AC:

4390

AN:

152364

Hom.:

106

Cov.:

AF XY:

0.0312

AC XY:

2323

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00577

Gnomad4 AMR

AF:

0.0267

Gnomad4 ASJ

AF:

0.0657

Gnomad4 EAS

AF:

0.110

Gnomad4 SAS

AF:

0.0364

Gnomad4 FIN

AF:

0.0631

Gnomad4 NFE

AF:

0.0290

Gnomad4 OTH

AF:

0.0388

Alfa

AF:

0.0303

Hom.:

Bravo

AF:

0.0257

TwinsUK

AF:

0.0272

AC:

101

ALSPAC

AF:

0.0272

AC:

105

ESP6500AA

AF:

0.00614

AC:

ESP6500EA

AF:

0.0276

AC:

237

ExAC

AF:

0.0384

AC:

4660

Asia WGS

AF:

0.0790

AC:

274

AN:

3478

EpiCase

AF:

0.0308

EpiControl

AF:

0.0319

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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

2.3

DANN

Benign

0.83

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0016

T;T

MutationTaster

Benign

0.00011

GERP RS

-7.6

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