rs17545383

chr5-161895250-C-G

Variant summary

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

The NM_001127644.2(GABRA1):c.857-416C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,826 control chromosomes in the GnomAD database, including 18,732 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 0.49 (18732 hom., cov: 31)
• Consequence: GABRA1 NM_001127644.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA1	NM_001127644.2	c.857-416C>G		intron_variant		ENST00000393943.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA1	ENST00000393943.10	c.857-416C>G		intron_variant		1	NM_001127644.2	P1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73740 AN: 151708 Hom.: 18708 Cov.: 31

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.485

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.486 AC: 73788 AN: 151826 Hom.: 18732 Cov.: 31 AF XY: 0.483 AC XY: 35816 AN XY: 74148

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.480

Alfa AF: 0.517 Hom.: 2600

Bravo AF: 0.485

Asia WGS AF: 0.342 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.73
Dann	Benign	0.56

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: rs17545383; hg19: chr5-161322256; COSMIC: COSV50100420; COSMIC: COSV50100420;