rs4363842

Positions:

• chr15-26774258-A-G
• chr15-26774258-A-T

Variant summary

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

The ENST00000541819.6(GABRB3):​c.249-1486T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 151,754 control chromosomes in the GnomAD database, including 60,787 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 0.89 (60787 hom., cov: 31)
• Consequence: GABRB3 ENST00000541819.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.854

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000541819.6	c.249-1486T>C		intron_variant		1		ENSP00000442408
GABRB3	ENST00000557641.5	n.453-1486T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135285 AN: 151638 Hom.: 60750 Cov.: 31

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.984

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.900

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

GnomAD4 genome AF: 0.892 AC: 135378 AN: 151754 Hom.: 60787 Cov.: 31 AF XY: 0.895 AC XY: 66424 AN XY: 74188

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.928

Gnomad4 ASJ AF: 0.951

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.984

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.932

Gnomad4 OTH AF: 0.901

Alfa AF: 0.903 Hom.: 7723

Bravo AF: 0.884

Asia WGS AF: 0.973 AC: 3382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4363842; hg19: chr15-27019405;