Variant chr1-2029250-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_000815.5(GABRD):c.831C>T(p.Pro277=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,563,878 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 34)

Exomes 𝑓: 0.000077 ( 1 hom. )

Consequence

GABRD
NM_000815.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.33

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049646497).

BP6

Variant 1-2029250-C-T is Benign according to our data. Variant chr1-2029250-C-T is described in ClinVar as [Benign]. Clinvar id is 460015.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.34 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GABRD	NM_000815.5 linkuse as main transcript	c.831C>T	p.Pro277=	synonymous_variant	7/9	ENST00000378585.7	NP_000806.2
GABRD	XM_017000936.2 linkuse as main transcript	c.1536C>T	p.Pro512=	synonymous_variant	6/8		XP_016856425.1
GABRD	XM_011541194.4 linkuse as main transcript	c.870C>T	p.Pro290=	synonymous_variant	7/9		XP_011539496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRD	ENST00000378585.7 linkuse as main transcript	c.831C>T	p.Pro277=	synonymous_variant	7/9	1	NM_000815.5	ENSP00000367848	P1

Frequencies

GnomAD3 genomes

AF:

0.000998

AC:

152

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000230

AC:

AN:

173744

Hom.:

AF XY:

0.000205

AC XY:

AN XY:

92512

show subpopulations

Gnomad AFR exome

AF:

0.00348

Gnomad AMR exome

AF:

0.0000764

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000792

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000138

Gnomad OTH exome

AF:

0.000206

GnomAD4 exome

AF:

0.0000772

AC:

109

AN:

1411496

Hom.:

Cov.:

AF XY:

0.0000774

AC XY:

AN XY:

697930

show subpopulations

Gnomad4 AFR exome

AF:

0.00265

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000272

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000735

Gnomad4 OTH exome

AF:

0.000153

GnomAD4 genome

AF:

0.000997

AC:

152

AN:

152382

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00361

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000615

Hom.:

Bravo

AF:

0.00106

ESP6500AA

AF:

0.00344

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000274

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Idiopathic generalized epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

2.0

DANN

Benign

0.78

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0050

MutationTaster

Benign

1.0

GERP RS

-3.4

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