1-2019509-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000815.5(GABRD):​c.68+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000383 in 704,402 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 29)
Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

GABRD
NM_000815.5 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.441
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 1-2019509-G-A is Benign according to our data. Variant chr1-2019509-G-A is described in ClinVar as [Benign]. Clinvar id is 1608248.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GABRDNM_000815.5 linkuse as main transcriptc.68+18G>A intron_variant ENST00000378585.7 NP_000806.2 O14764A8K496

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GABRDENST00000378585.7 linkuse as main transcriptc.68+18G>A intron_variant 1 NM_000815.5 ENSP00000367848.4 O14764

Frequencies

GnomAD3 genomes
AF:
0.00115
AC:
169
AN:
146366
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00397
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000406
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000151
Gnomad OTH
AF:
0.000998
GnomAD4 exome
AF:
0.000181
AC:
101
AN:
557926
Hom.:
1
Cov.:
6
AF XY:
0.000178
AC XY:
47
AN XY:
263890
show subpopulations
Gnomad4 AFR exome
AF:
0.00746
Gnomad4 AMR exome
AF:
0.000322
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000205
Gnomad4 OTH exome
AF:
0.000855
GnomAD4 genome
AF:
0.00115
AC:
169
AN:
146476
Hom.:
0
Cov.:
29
AF XY:
0.000952
AC XY:
68
AN XY:
71444
show subpopulations
Gnomad4 AFR
AF:
0.00396
Gnomad4 AMR
AF:
0.000405
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000152
Gnomad4 OTH
AF:
0.000986
Alfa
AF:
0.000641
Hom.:
0
Bravo
AF:
0.00142

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 15, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
13
DANN
Benign
0.90

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.

Other links and lift over

dbSNP: rs952639317; hg19: chr1-1950948; API