rs4477673

Positions:

• chr15-26817359-T-C

Variant summary

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

The ENST00000541819.6(GABRB3):​c.201-945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,686 control chromosomes in the GnomAD database, including 11,321 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 0.37 (11321 hom., cov: 30)
• Consequence: GABRB3 ENST00000541819.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.487 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.201-945A>G		intron_variant		1		ENSP00000442408

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56281 AN: 151568 Hom.: 11292 Cov.: 30

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.372 AC: 56363 AN: 151686 Hom.: 11321 Cov.: 30 AF XY: 0.370 AC XY: 27447 AN XY: 74090

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.408

Alfa AF: 0.348 Hom.: 2257

Bravo AF: 0.397

Asia WGS AF: 0.437 AC: 1521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.0
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4477673; hg19: chr15-27062506;