15-26560917-T-C

Position:

chr15-26560917-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0120

Variant links:

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]

GABRB3 links:

GABRB3 (HGNC:):

GABRB3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
GABRB3	NM_000814.6 linkuse as main transcript	c.1080+15A>G		intron_variant		ENST00000311550.10	NP_000805.1	P28472-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000311550.10 linkuse as main transcript	c.1080+15A>G		intron_variant		1	NM_000814.6	ENSP00000308725.5		P28472-1

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53536

AN:

151876

Hom.:

10550

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.299

AC XY:

217214

AN XY:

726734

show subpopulations

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.:

AF XY:

0.355

AC XY:

26348

AN XY:

74300

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 06, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 31, 2016	- -

Developmental and epileptic encephalopathy, 43

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over