rs4906902

Variant names:

• chr15-26774621-A-G
• rs4906902
• ENST00000541819.6:c.249-1849T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_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. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2626 hom., cov: 33)
• Consequence: GABRB3 ENST00000541819.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 15-26774621-A-G is Benign according to our data. Variant chr15-26774621-A-G is described in ClinVar as [Benign]. Clinvar id is 3762491.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000541819.6	c.249-1849T>C		intron_variant	Intron 2 of 9	1		ENSP00000442408.2
GABRB3	ENST00000557641.5	n.453-1849T>C		intron_variant	Intron 1 of 3	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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epilepsy, childhood absence, susceptibility to, 1;C2677087:Epilepsy, childhood absence, susceptibility to, 5 Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;