15-26625455-C-T

Variant names:

• chr15-26625455-C-T
• rs12438141
• NM_000814.6:c.241-3921G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000814.6(GABRB3):​c.241-3921G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 983,684 control chromosomes in the GnomAD database, including 11,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2187 hom., cov: 32)
  • Exomes 𝑓: 0.15 (9618 hom.)
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.608

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-26625455-C-T is Benign according to our data. Variant chr15-26625455-C-T is described in ClinVar as [Benign]. Clinvar id is 3256811.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB3	NM_000814.6	c.241-3921G>A		intron_variant	Intron 3 of 8	ENST00000311550.10	NP_000805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000311550.10	c.241-3921G>A		intron_variant	Intron 3 of 8	1	NM_000814.6	ENSP00000308725.5

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25523 AN: 151944 Hom.: 2186 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0532

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.151 AC: 125224 AN: 831622 Hom.: 9618 Cov.: 25 AF XY: 0.151 AC XY: 57937 AN XY: 384070

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.0485

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.168 AC: 25537 AN: 152062 Hom.: 2187 Cov.: 32 AF XY: 0.167 AC XY: 12388 AN XY: 74340

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.0538

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.180

Alfa AF: 0.161 Hom.: 647

Bravo AF: 0.171

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jul 31, 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 39% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 36. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.5
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs12438141; hg19: chr15-26870602;