rs4340950

Positions:

• chr5-161853637-A-G
• chr5-161853637-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127644.2(GABRA1):​c.75-521A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 151,882 control chromosomes in the GnomAD database, including 1,963 homozygotes. 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: 𝑓 0.15 (1963 hom., cov: 32)
  • Exomes 𝑓: 0.056 (0 hom.)
• Consequence: GABRA1 NM_001127644.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.798

Genes affected

GABRA1 (HGNC:4075): (gamma-aminobutyric acid type A receptor subunit alpha1) This gene encodes a gamma-aminobutyric acid (GABA) receptor. 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. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene cause juvenile myoclonic epilepsy and childhood absence epilepsy type 4. Multiple transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA1	NM_001127644.2	c.75-521A>G		intron_variant		ENST00000393943.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA1	ENST00000393943.10	c.75-521A>G		intron_variant		1	NM_001127644.2	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22311 AN: 151692 Hom.: 1962 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0823

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.0556 AC: 4 AN: 72 Hom.: 0 Cov.: 0 AF XY: 0.0652 AC XY: 3 AN XY: 46

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.0333

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.147 AC: 22315 AN: 151810 Hom.: 1963 Cov.: 32 AF XY: 0.149 AC XY: 11043 AN XY: 74222

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.0822

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.128

Alfa AF: 0.110 Hom.: 957

Bravo AF: 0.148

Asia WGS AF: 0.227 AC: 785 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	17
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs4340950; hg19: chr5-161280643;