rs2229110

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.330T>C(p.Gly110Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 1,612,716 control chromosomes in the GnomAD database, including 327,885 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 33159 hom., cov: 34)

Exomes 𝑓: 0.63 ( 294726 hom. )

Consequence

GABRD
NM_000815.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.22

Publications

21 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=9.98378E-7).

BP6

Variant 1-2025598-T-C is Benign according to our data. Variant chr1-2025598-T-C is described in ClinVar as Benign. ClinVar VariationId is 256823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRD	NM_000815.5 link	c.330T>C	p.Gly110Gly	synonymous_variant	Exon 4 of 9	ENST00000378585.7	NP_000806.2	O14764A8K496
GABRD	XM_017000936.2 link	c.1035T>C	p.Gly345Gly	synonymous_variant	Exon 3 of 8		XP_016856425.1
GABRD	XM_011541194.4 link	c.369T>C	p.Gly123Gly	synonymous_variant	Exon 4 of 9		XP_011539496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRD	ENST00000378585.7 link	c.330T>C	p.Gly110Gly	synonymous_variant	Exon 4 of 9	1	NM_000815.5	ENSP00000367848.4		O14764

Frequencies

GnomAD3 genomes

AF:

0.655

AC:

99494

AN:

151996

Hom.:

33171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.729

Gnomad AMI

AF:

0.792

Gnomad AMR

AF:

0.600

Gnomad ASJ

AF:

0.712

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.466

Gnomad FIN

AF:

0.641

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.656

Gnomad OTH

AF:

0.662

GnomAD2 exomes

AF:

0.588

AC:

147340

AN:

250576

AF XY:

0.589

show subpopulations

Gnomad AFR exome

AF:

0.730

Gnomad AMR exome

AF:

0.474

Gnomad ASJ exome

AF:

0.689

Gnomad EAS exome

AF:

0.314

Gnomad FIN exome

AF:

0.638

Gnomad NFE exome

AF:

0.657

Gnomad OTH exome

AF:

0.629

GnomAD4 exome

AF:

0.630

AC:

920909

AN:

1460604

Hom.:

294726

Cov.:

AF XY:

0.627

AC XY:

455681

AN XY:

726602

show subpopulations

African (AFR)

AF:

0.731

AC:

24481

AN:

33476

American (AMR)

AF:

0.487

AC:

21773

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.696

AC:

18198

AN:

26132

East Asian (EAS)

AF:

0.360

AC:

14303

AN:

39696

South Asian (SAS)

AF:

0.474

AC:

40907

AN:

86256

European-Finnish (FIN)

AF:

0.640

AC:

33484

AN:

52304

Middle Eastern (MID)

AF:

0.708

AC:

4084

AN:

5768

European-Non Finnish (NFE)

AF:

0.653

AC:

725697

AN:

1111880

Other (OTH)

AF:

0.629

AC:

37982

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

20647

41294

61942

82589

103236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18814

37628

56442

75256

94070

<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:

0.654

AC:

99507

AN:

152112

Hom.:

33159

Cov.:

AF XY:

0.647

AC XY:

48096

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.728

AC:

30232

AN:

41514

American (AMR)

AF:

0.599

AC:

9158

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.712

AC:

2469

AN:

3470

East Asian (EAS)

AF:

0.341

AC:

1757

AN:

5160

South Asian (SAS)

AF:

0.464

AC:

2235

AN:

4818

European-Finnish (FIN)

AF:

0.641

AC:

6780

AN:

10584

Middle Eastern (MID)

AF:

0.736

AC:

215

AN:

292

European-Non Finnish (NFE)

AF:

0.656

AC:

44549

AN:

67960

Other (OTH)

AF:

0.658

AC:

1390

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1812

3624

5435

7247

9059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.666

Hom.:

15282

Bravo

AF:

0.654

TwinsUK

AF:

0.668

AC:

2477

ALSPAC

AF:

0.653

AC:

2516

ESP6500AA

AF:

0.731

AC:

3220

ESP6500EA

AF:

0.660

AC:

5680

ExAC

AF:

0.592

AC:

71860

Asia WGS

AF:

0.414

AC:

1444

AN:

3478

EpiCase

AF:

0.668

EpiControl

AF:

0.667

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 06, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Epilepsy, idiopathic generalized, susceptibility to, 10

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Idiopathic generalized epilepsy

Benign:1

Feb 04, 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

Benign

0.23

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.73

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.16

MetaRNN

Benign

0.0000010

PhyloP100

-1.2

GERP RS

2.5

PromoterAI

0.049

Neutral

(source)

Mutation Taster

=100/0

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

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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