Variant 1-2025673-C-T 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.405C>T(p.His135His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,613,010 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 34)

Exomes 𝑓: 0.0035 ( 14 hom. )

Consequence

GABRD
NM_000815.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.265

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 (BayesDel_noAF=-0.57).

BP6

Variant 1-2025673-C-T is Benign according to our data. Variant chr1-2025673-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 460009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-2025673-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.265 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRD	NM_000815.5 linkuse as main transcript	c.405C>T	p.His135His	synonymous_variant	4/9	ENST00000378585.7	NP_000806.2	O14764A8K496
GABRD	XM_017000936.2 linkuse as main transcript	c.1110C>T	p.His370His	synonymous_variant	3/8		XP_016856425.1
GABRD	XM_011541194.4 linkuse as main transcript	c.444C>T	p.His148His	synonymous_variant	4/9		XP_011539496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRD	ENST00000378585.7 linkuse as main transcript	c.405C>T	p.His135His	synonymous_variant	4/9	1	NM_000815.5	ENSP00000367848.4		O14764

Frequencies

GnomAD3 genomes

AF:

0.00254

AC:

386

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00367

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00233

AC:

583

AN:

250520

Hom.:

AF XY:

0.00228

AC XY:

309

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.000598

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00402

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00346

AC:

5052

AN:

1460642

Hom.:

Cov.:

AF XY:

0.00331

AC XY:

2402

AN XY:

726630

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00206

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.000632

Gnomad4 NFE exome

AF:

0.00418

Gnomad4 OTH exome

AF:

0.00359

GnomAD4 genome

AF:

0.00253

AC:

386

AN:

152368

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

177

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00139

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00367

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00298

Hom.:

Bravo

AF:

0.00299

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00407

AC:

ExAC

AF:

0.00261

AC:

317

EpiCase

AF:

0.00322

EpiControl

AF:

0.00445

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epilepsy, idiopathic generalized, susceptibility to, 10

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 25, 2022

- -

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

-0.57

CADD

Benign

1.0

DANN

Benign

0.70

FATHMM_MKL

Benign

0.22

GERP RS

-4.7

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