5-161878065-C-T

Position:

• chr5-161878065-C-T

Variant summary

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

The NM_001127644.2(GABRA1):​c.559+2423C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,006 control chromosomes in the GnomAD database, including 20,833 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 0.51 (20833 hom., cov: 33)
• Consequence: GABRA1 NM_001127644.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA1	NM_001127644.2	c.559+2423C>T		intron_variant		ENST00000393943.10	NP_001121116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA1	ENST00000393943.10	c.559+2423C>T		intron_variant		1	NM_001127644.2	ENSP00000377517	P1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77972 AN: 151888 Hom.: 20800 Cov.: 33

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.513 AC: 78040 AN: 152006 Hom.: 20833 Cov.: 33 AF XY: 0.517 AC XY: 38380 AN XY: 74288

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.520

Alfa AF: 0.456 Hom.: 29785

Bravo AF: 0.514

Asia WGS AF: 0.657 AC: 2283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.1
DANN	Benign	0.54

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: rs6878494; hg19: chr5-161305071;