1-2030027-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000815.5(GABRD):c.1104C>T(p.Ala368Ala) 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

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics, ClinGen
epilepsy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
epilepsy, idiopathic generalized, susceptibility to, 10
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

GABRD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 460004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein
GABRD	NM_000815.5 link	c.1104C>T	p.Ala368Ala	synonymous_variant	Exon 9 of 9	ENST00000378585.7	NP_000806.2
GABRD	XM_017000936.2 link	c.1809C>T	p.Ala603Ala	synonymous_variant	Exon 8 of 8		XP_016856425.1
GABRD	XM_011541194.4 link	c.1143C>T	p.Ala381Ala	synonymous_variant	Exon 9 of 9		XP_011539496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRD	ENST00000378585.7 link	c.1104C>T	p.Ala368Ala	synonymous_variant	Exon 9 of 9	1	NM_000815.5	ENSP00000367848.4

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

GnomAD2 exomes

AF:

0.0396

AC:

9827

AN:

248252

AF XY:

0.0401

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 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

African (AFR)

AF:

0.00526

AC:

176

AN:

33474

American (AMR)

AF:

0.0236

AC:

1056

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.0616

AC:

1608

AN:

26116

East Asian (EAS)

AF:

0.101

AC:

4007

AN:

39692

South Asian (SAS)

AF:

0.0335

AC:

2889

AN:

86238

European-Finnish (FIN)

AF:

0.0632

AC:

3297

AN:

52128

Middle Eastern (MID)

AF:

0.0446

AC:

257

AN:

5768

European-Non Finnish (NFE)

AF:

0.0285

AC:

31735

AN:

1111836

Other (OTH)

AF:

0.0373

AC:

2252

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

2658

5316

7973

10631

13289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1248

2496

3744

4992

6240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0288

AC:

4390

AN:

152364

Hom.:

106

Cov.:

AF XY:

0.0312

AC XY:

2323

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00577

AC:

240

AN:

41590

American (AMR)

AF:

0.0267

AC:

409

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0657

AC:

228

AN:

3472

East Asian (EAS)

AF:

0.110

AC:

569

AN:

5186

South Asian (SAS)

AF:

0.0364

AC:

176

AN:

4830

European-Finnish (FIN)

AF:

0.0631

AC:

671

AN:

10628

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0290

AC:

1971

AN:

68026

Other (OTH)

AF:

0.0388

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

236

472

708

944

1180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Idiopathic generalized epilepsy

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_noAF

Benign

-0.57

CADD

Benign

2.3

(source)

DANN

Benign

0.83

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0016

T;T

PhyloP100

-3.3

GERP RS

-7.6

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over