1-2019508-C-G

Position:

• chr1-2019508-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000815.5(GABRD):​c.68+17C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00063 in 1,098,548 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00063 (2 hom.)
• Consequence: GABRD NM_000815.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.28

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-2019508-C-G is Benign according to our data. Variant chr1-2019508-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1605999.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRD	NM_000815.5	c.68+17C>G		intron_variant		ENST00000378585.7	NP_000806.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRD	ENST00000378585.7	c.68+17C>G		intron_variant		1	NM_000815.5	ENSP00000367848.4

Frequencies

GnomAD3 genomes AF: 0.000620 AC: 88 AN: 141906 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000984

Gnomad ASJ AF: 0.00179

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000535

Gnomad MID AF: 0.00806

Gnomad NFE AF: 0.000835

Gnomad OTH AF: 0.00157

GnomAD4 exome AF: 0.000631 AC: 604 AN: 956530 Hom.: 2 Cov.: 24 AF XY: 0.000641 AC XY: 288 AN XY: 448952

Gnomad4 AFR exome AF: 0.0000531

Gnomad4 AMR exome AF: 0.000218

Gnomad4 ASJ exome AF: 0.00152

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000722

Gnomad4 FIN exome AF: 0.000526

Gnomad4 NFE exome AF: 0.000643

Gnomad4 OTH exome AF: 0.000655

GnomAD4 genome AF: 0.000620 AC: 88 AN: 142018 Hom.: 0 Cov.: 29 AF XY: 0.000520 AC XY: 36 AN XY: 69254

Gnomad4 AFR AF: 0.000103

Gnomad4 AMR AF: 0.000982

Gnomad4 ASJ AF: 0.00179

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000535

Gnomad4 NFE AF: 0.000835

Gnomad4 OTH AF: 0.00155

Alfa AF: 0.000594 Hom.: 0

Bravo AF: 0.000582

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Idiopathic generalized epilepsy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 19, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.52

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

Other links and lift over

dbSNP: rs868634453; hg19: chr1-1950947;