15-26774455-C-T

Variant names:

• chr15-26774455-C-T
• rs8179184
• ENST00000541819.6:c.249-1683G>A

Variant summary

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

The ENST00000541819.6(GABRB3):​c.249-1683G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,208 control chromosomes in the GnomAD database, including 2,104 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 0.14 (2104 hom., cov: 33)
• Consequence: GABRB3 ENST00000541819.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.962

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000541819.6	c.249-1683G>A		intron_variant	Intron 2 of 9	1		ENSP00000442408.2
GABRB3	ENST00000557641.5	n.453-1683G>A		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20924 AN: 152090 Hom.: 2097 Cov.: 33

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.138 AC: 20942 AN: 152208 Hom.: 2104 Cov.: 33 AF XY: 0.146 AC XY: 10840 AN XY: 74418

Gnomad4 AFR AF: 0.0352

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.138

Alfa AF: 0.133 Hom.: 337

Bravo AF: 0.142

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.64
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8179184; hg19: chr15-27019602;