15-26560917-T-C

Variant names:

• chr15-26560917-T-C
• rs3751582
• NM_000814.6:c.1080+15A>G

Variant summary

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

The NM_000814.6(GABRB3):​c.1080+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,612,842 control chromosomes in the GnomAD database, including 82,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10564 hom., cov: 33)
  • Exomes 𝑓: 0.30 (71939 hom.)
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.0120

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=-0.92).
• BP6: Variant 15-26560917-T-C is Benign according to our data. Variant chr15-26560917-T-C is described in ClinVar as [Benign]. Clinvar id is 256818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB3	NM_000814.6	c.1080+15A>G		intron_variant	Intron 8 of 8	ENST00000311550.10	NP_000805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000311550.10	c.1080+15A>G		intron_variant	Intron 8 of 8	1	NM_000814.6	ENSP00000308725.5

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53536 AN: 151876 Hom.: 10550 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.324

GnomAD3 exomes AF: 0.344 AC: 86488 AN: 251448 Hom.: 17278 AF XY: 0.337 AC XY: 45820 AN XY: 135906

Gnomad AFR exome AF: 0.488

Gnomad AMR exome AF: 0.355

Gnomad ASJ exome AF: 0.278

Gnomad EAS exome AF: 0.756

Gnomad SAS exome AF: 0.383

Gnomad FIN exome AF: 0.287

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.314

GnomAD4 exome AF: 0.298 AC: 435670 AN: 1460848 Hom.: 71939 Cov.: 41 AF XY: 0.299 AC XY: 217214 AN XY: 726734

Gnomad4 AFR exome AF: 0.490

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.775

Gnomad4 SAS exome AF: 0.380

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.324

GnomAD4 genome AF: 0.353 AC: 53602 AN: 151994 Hom.: 10564 Cov.: 33 AF XY: 0.355 AC XY: 26348 AN XY: 74300

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.323

Alfa AF: 0.283 Hom.: 10901

Bravo AF: 0.363

Asia WGS AF: 0.529 AC: 1839 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 31, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 06, 2016

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. -

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 51% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 47. Only high quality variants are reported. -

Developmental and epileptic encephalopathy, 43 Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.25
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3751582; hg19: chr15-26806064; COSMIC: COSV54680164; COSMIC: COSV54680164;