rs4906902

Positions:

• chr15-26774621-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000541819.6(GABRB3):​c.249-1849T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,194 control chromosomes in the GnomAD database, including 2,626 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 0.16 (2626 hom., cov: 33)
• Consequence: GABRB3 ENST00000541819.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.313 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.249-1849T>C		intron_variant		1		ENSP00000442408
GABRB3	ENST00000557641.5	n.453-1849T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24108 AN: 152076 Hom.: 2616 Cov.: 33

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.158 AC: 24122 AN: 152194 Hom.: 2626 Cov.: 33 AF XY: 0.166 AC XY: 12358 AN XY: 74392

Gnomad4 AFR AF: 0.0393

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.166

Alfa AF: 0.153 Hom.: 365

Bravo AF: 0.162

Asia WGS AF: 0.267 AC: 927 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4906902; hg19: chr15-27019768;