rs7173687

chr15-26871571-G-Achr15-26871571-G-Cchr15-26871571-G-T

Variant summary

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

The NM_000810.4(GABRA5):c.86+2237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 151,932 control chromosomes in the GnomAD database, including 31,270 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 0.64 (31270 hom., cov: 32)
• Consequence: GABRA5 NM_000810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351

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]

GABRB3 (HGNC:4083): (gamma-aminobutyric acid type A receptor subunit beta3) This gene encodes a member of the ligand-gated ionic channel family. The encoded protein is one the subunits of a multi-subunit chloride channel that serves as the receptor for gamma-aminobutyric acid, a major inhibitory neurotransmitter of the mammalian nervous system. This gene is located on the long arm of chromosome 15 in a cluster with two other genes encoding related subunits of the family. This gene may be associated with the pathogenesis of several disorders including Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA5	NM_000810.4	c.86+2237G>A		intron_variant		ENST00000335625.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA5	ENST00000335625.10	c.86+2237G>A		intron_variant		1	NM_000810.4	P1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97365 AN: 151816 Hom.: 31261 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.689

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.641 AC: 97406 AN: 151932 Hom.: 31270 Cov.: 32 AF XY: 0.638 AC XY: 47382 AN XY: 74254

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.644

Alfa AF: 0.643 Hom.: 40060

Bravo AF: 0.644

Asia WGS AF: 0.583 AC: 2028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.18
Dann	Benign	0.55

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: rs7173687; hg19: chr15-27116718;