rs1426217

chr15-26575978-A-G

Variant summary

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

The NM_000814.6(GABRB3):c.682+4341T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,008 control chromosomes in the GnomAD database, including 15,921 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 0.45 (15921 hom., cov: 33)
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB3	NM_000814.6	c.682+4341T>C		intron_variant		ENST00000311550.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB3	ENST00000311550.10	c.682+4341T>C		intron_variant		1	NM_000814.6	P1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68551 AN: 151890 Hom.: 15896 Cov.: 33

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.451 AC: 68617 AN: 152008 Hom.: 15921 Cov.: 33 AF XY: 0.447 AC XY: 33193 AN XY: 74292

Gnomad4 AFR AF: 0.533

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.439

Alfa AF: 0.429 Hom.: 28854

Bravo AF: 0.455

Asia WGS AF: 0.302 AC: 1051 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	0.84
Dann	Benign	0.21

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: rs1426217; hg19: chr15-26821125;