15-26773790-G-C

Variant names:

• chr15-26773790-G-C
• rs20317
• ENST00000541819.6:c.249-1018C>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000541819.6(GABRB3):​c.249-1018C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,443,350 control chromosomes in the GnomAD database, including 25,289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2446 hom., cov: 29)
  • Exomes 𝑓: 0.18 (22843 hom.)
• Consequence: GABRB3 ENST00000541819.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.43

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 15-26773790-G-C is Benign according to our data. Variant chr15-26773790-G-C is described in ClinVar as [Benign]. Clinvar id is 681728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB3	NM_021912.5	c.-66C>G		upstream_gene_variant			NP_068712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000541819.6	c.249-1018C>G		intron_variant	Intron 2 of 9	1		ENSP00000442408.2
GABRB3	ENST00000638099.1	c.-20+153C>G		intron_variant	Intron 1 of 8	5		ENSP00000490678.1
GABRB3	ENST00000557641.5	n.453-1018C>G		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.152 AC: 22772 AN: 150116 Hom.: 2436 Cov.: 29

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.178 AC: 230764 AN: 1293124 Hom.: 22843 Cov.: 19 AF XY: 0.180 AC XY: 115507 AN XY: 641708

Gnomad4 AFR exome AF: 0.0301

Gnomad4 AMR exome AF: 0.384

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.337

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.152 AC: 22787 AN: 150226 Hom.: 2446 Cov.: 29 AF XY: 0.158 AC XY: 11564 AN XY: 73172

Gnomad4 AFR AF: 0.0373

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.158

Alfa AF: 0.0547 Hom.: 77

Bravo AF: 0.160

Asia WGS AF: 0.247 AC: 836 AN: 3384

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 29. Only high quality variants are reported. -

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

Jan 22, 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	-0.84
CADD	Benign	0.65
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs20317; hg19: chr15-27018937;