15-26794935-T-G

Position:

• chr15-26794935-T-G

Variant summary

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

The ENST00000541819.6(GABRB3):​c.248+21432A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,060 control chromosomes in the GnomAD database, including 16,729 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 0.43 (16729 hom., cov: 32)
• Consequence: GABRB3 ENST00000541819.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.602 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.248+21432A>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65303 AN: 151942 Hom.: 16720 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.430 AC: 65315 AN: 152060 Hom.: 16729 Cov.: 32 AF XY: 0.439 AC XY: 32601 AN XY: 74316

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.480

Alfa AF: 0.503 Hom.: 9107

Bravo AF: 0.423

Asia WGS AF: 0.621 AC: 2158 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.24
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4906908; hg19: chr15-27040082;