rs8179186

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_000814.6(GABRB3):c.240+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,603,122 control chromosomes in the GnomAD database, including 22,136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2039 hom., cov: 34)

Exomes 𝑓: 0.15 ( 20097 hom. )

Consequence

GABRB3
NM_000814.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.680

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:

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=-0.78).

BP6

Variant 15-26772389-G-A is Benign according to our data. Variant chr15-26772389-G-A is described in ClinVar as [Benign]. Clinvar id is 256819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GABRB3	NM_000814.6 link	c.240+13C>T	intron_variant	Intron 3 of 8	ENST00000311550.10	NP_000805.1	P28472-1
GABRB3	NM_021912.5 link	c.240+13C>T	intron_variant	Intron 3 of 8		NP_068712.1	P28472-2B2RCW8X5DQY4
GABRB3	NM_001278631.2 link	c.-112+13C>T	intron_variant	Intron 3 of 9		NP_001265560.1	P28472-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000311550.10 link	c.240+13C>T		intron_variant	Intron 3 of 8	1	NM_000814.6	ENSP00000308725.5		P28472-1

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20639

AN:

152090

Hom.:

2033

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0350

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.288

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.316

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.137

GnomAD3 exomes

AF:

0.191

AC:

44799

AN:

234610

Hom.:

5580

AF XY:

0.185

AC XY:

23556

AN XY:

127636

show subpopulations

Gnomad AFR exome

AF:

0.0300

Gnomad AMR exome

AF:

0.388

Gnomad ASJ exome

AF:

0.0998

Gnomad EAS exome

AF:

0.314

Gnomad SAS exome

AF:

0.208

Gnomad FIN exome

AF:

0.173

Gnomad NFE exome

AF:

0.139

Gnomad OTH exome

AF:

0.177

GnomAD4 exome

AF:

0.154

AC:

223505

AN:

1450924

Hom.:

20097

Cov.:

AF XY:

0.155

AC XY:

111748

AN XY:

721278

show subpopulations

Gnomad4 AFR exome

AF:

0.0262

Gnomad4 AMR exome

AF:

0.377

Gnomad4 ASJ exome

AF:

0.0982

Gnomad4 EAS exome

AF:

0.336

Gnomad4 SAS exome

AF:

0.204

Gnomad4 FIN exome

AF:

0.172

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.148

GnomAD4 genome

AF:

0.136

AC:

20655

AN:

152198

Hom.:

2039

Cov.:

AF XY:

0.144

AC XY:

10690

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0349

Gnomad4 AMR

AF:

0.289

Gnomad4 ASJ

AF:

0.100

Gnomad4 EAS

AF:

0.315

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.140

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.0830

Hom.:

149

Bravo

AF:

0.139

Asia WGS

AF:

0.256

AC:

889

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 08, 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 53% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 49. Only high quality variants are reported. -

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

-0.78

CADD

Benign

DANN

Benign

0.92

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

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