rs140683

chr15-26943188-T-Achr15-26943188-T-Cchr15-26943188-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000810.4(GABRA5):c.878-27T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,533,578 control chromosomes in the GnomAD database, including 144,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (10921 hom., cov: 34)
  • Exomes 𝑓: 0.43 (133787 hom.)
• Consequence: GABRA5 NM_000810.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.129

Genes affected

GABRA5 (HGNC:4079): (gamma-aminobutyric acid type A receptor subunit alpha5) 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. At least 16 distinct subunits of GABA-A receptors have been identified. Transcript variants utilizing three different alternative non-coding first exons have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 15-26943188-T-A is Benign according to our data. Variant chr15-26943188-T-A is described in ClinVar as [Benign]. Clinvar id is 1285289.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA5	NM_000810.4	c.878-27T>A		intron_variant		ENST00000335625.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA5	ENST00000335625.10	c.878-27T>A		intron_variant		1	NM_000810.4	P1
GABRA5	ENST00000355395.9	c.878-27T>A		intron_variant		5		P1
GABRA5	ENST00000400081.7	c.878-27T>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55925 AN: 152032 Hom.: 10927 Cov.: 34

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.355

GnomAD3 exomes AF: 0.369 AC: 53836 AN: 145890 Hom.: 10651 AF XY: 0.373 AC XY: 28965 AN XY: 77650

Gnomad AFR exome AF: 0.252

Gnomad AMR exome AF: 0.280

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.191

Gnomad SAS exome AF: 0.358

Gnomad FIN exome AF: 0.421

Gnomad NFE exome AF: 0.451

Gnomad OTH exome AF: 0.390

GnomAD4 exome AF: 0.435 AC: 600267 AN: 1381430 Hom.: 133787 Cov.: 27 AF XY: 0.433 AC XY: 295013 AN XY: 680658

Gnomad4 AFR exome AF: 0.251

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.359

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.361

Gnomad4 FIN exome AF: 0.426

Gnomad4 NFE exome AF: 0.462

Gnomad4 OTH exome AF: 0.402

GnomAD4 genome AF: 0.368 AC: 55936 AN: 152148 Hom.: 10921 Cov.: 34 AF XY: 0.364 AC XY: 27093 AN XY: 74402

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.353

Alfa AF: 0.397 Hom.: 2281

Bravo AF: 0.357

Asia WGS AF: 0.281 AC: 980 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 79 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.6
Dann	Benign	0.53

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: rs140683; hg19: chr15-27188335; COSMIC: COSV59487341; COSMIC: COSV59487341;