GeneBe

1-2019444-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_000815.5(GABRD):​c.21G>T​(p.Leu7Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 27)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

GABRD
NM_000815.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.79
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]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 1-2019444-G-T is Benign according to our data. Variant chr1-2019444-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2125132.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.79 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GABRDNM_000815.5 linkc.21G>T p.Leu7Leu synonymous_variant Exon 1 of 9 ENST00000378585.7 NP_000806.2 O14764A8K496

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GABRDENST00000378585.7 linkc.21G>T p.Leu7Leu synonymous_variant Exon 1 of 9 1 NM_000815.5 ENSP00000367848.4 O14764

Frequencies

GnomAD3 genomes
Cov.:
27
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
958908
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
453290
African (AFR)
AF:
0.00
AC:
0
AN:
18574
American (AMR)
AF:
0.00
AC:
0
AN:
4682
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
8976
East Asian (EAS)
AF:
0.00
AC:
0
AN:
12904
South Asian (SAS)
AF:
0.00
AC:
0
AN:
21222
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
12404
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2234
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
843150
Other (OTH)
AF:
0.00
AC:
0
AN:
34762
GnomAD4 genome
Cov.:
27

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Idiopathic generalized epilepsy Benign:1
May 07, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
11
DANN
Benign
0.88
PhyloP100
1.8
PromoterAI
-0.030
Neutral
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs1484032223; hg19: chr1-1950883; API