rs12593579

Positions:

• chr15-26742985-A-C
• chr15-26742985-A-G
• chr15-26742985-A-T

Variant summary

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

The NM_000814.6(GABRB3):​c.240+29417T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 130,886 control chromosomes in the GnomAD database, including 2,703 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 0.20 (2703 hom., cov: 26)
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

Genes affected

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRB3	NM_000814.6	c.240+29417T>G		intron_variant		ENST00000311550.10	NP_000805.1
GABRB3	NM_001278631.2	c.-112+29417T>G		intron_variant			NP_001265560.1
GABRB3	NM_021912.5	c.240+29417T>G		intron_variant			NP_068712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000311550.10	c.240+29417T>G		intron_variant		1	NM_000814.6	ENSP00000308725	P1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 25911 AN: 130842 Hom.: 2705 Cov.: 26

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.314

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.198 AC: 25917 AN: 130886 Hom.: 2703 Cov.: 26 AF XY: 0.205 AC XY: 12507 AN XY: 61044

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.189

Alfa AF: 0.0538 Hom.: 51

Bravo AF: 0.187

Asia WGS AF: 0.217 AC: 740 AN: 3406

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.8
DANN	Benign	0.17

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: rs12593579; hg19: chr15-26988132;