rs1164917987

Variant names:

• chr1-2019477-G-A
• rs1164917987
• NM_000815.5:c.54G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-2019477-G-A
• chr1-2019477-G-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000815.5(GABRD):​c.54G>A​(p.Gln18Gln) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GABRD NM_000815.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.626
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics, ClinGen
• epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• epilepsy, idiopathic generalized, susceptibility to, 10

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=0.626 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRD	NM_000815.5	c.54G>A	p.Gln18Gln	synonymous_variant	Exon 1 of 9	ENST00000378585.7	NP_000806.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRD	ENST00000378585.7	c.54G>A	p.Gln18Gln	synonymous_variant	Exon 1 of 9	1	NM_000815.5	ENSP00000367848.4

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 965270 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 453744

African (AFR) AF: 0.00 AC: 0 AN: 18992

American (AMR) AF: 0.00 AC: 0 AN: 4774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9422

East Asian (EAS) AF: 0.00 AC: 0 AN: 14888

South Asian (SAS) AF: 0.00 AC: 0 AN: 18550

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 847106

Other (OTH) AF: 0.00 AC: 0 AN: 35534

GnomAD4 genome Cov.: 27

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.2
DANN	Benign	0.81
PhyloP100		0.63
PromoterAI		0.0071	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

Other links and lift over

dbSNP: rs1164917987; hg19: chr1-1950916;