15-26818391-T-C

Variant summary

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

The ENST00000541819.6(GABRB3):c.201-1977A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 150,914 control chromosomes in the GnomAD database, including 20,625 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 0.48 (20625 hom., cov: 28)
• Consequence: GABRB3 ENST00000541819.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.367

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB3	ENST00000541819.6	c.201-1977A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 71974 AN: 150798 Hom.: 20627 Cov.: 28

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.477 AC: 71975 AN: 150914 Hom.: 20625 Cov.: 28 AF XY: 0.479 AC XY: 35294 AN XY: 73654

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.481

Alfa AF: 0.533 Hom.: 2929

Bravo AF: 0.443

Asia WGS AF: 0.471 AC: 1635 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.8
Dann	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4412952; hg19: chr15-27063538;