rs75015217

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000814.6(GABRB3):​c.682+20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,614,074 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0024 ( 3 hom. )

Consequence

GABRB3
NM_000814.6 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.16
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 15-26580299-T-C is Benign according to our data. Variant chr15-26580299-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 382825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 277 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GABRB3NM_000814.6 linkuse as main transcriptc.682+20A>G intron_variant ENST00000311550.10 NP_000805.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GABRB3ENST00000311550.10 linkuse as main transcriptc.682+20A>G intron_variant 1 NM_000814.6 ENSP00000308725 P1P28472-1

Frequencies

GnomAD3 genomes
AF:
0.00182
AC:
277
AN:
152134
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000531
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00306
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00169
AC:
425
AN:
251186
Hom.:
2
AF XY:
0.00172
AC XY:
233
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.00142
Gnomad ASJ exome
AF:
0.000596
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00111
Gnomad NFE exome
AF:
0.00289
Gnomad OTH exome
AF:
0.00179
GnomAD4 exome
AF:
0.00243
AC:
3554
AN:
1461822
Hom.:
3
Cov.:
31
AF XY:
0.00236
AC XY:
1719
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.00159
Gnomad4 ASJ exome
AF:
0.000765
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00146
Gnomad4 NFE exome
AF:
0.00295
Gnomad4 OTH exome
AF:
0.00162
GnomAD4 genome
AF:
0.00182
AC:
277
AN:
152252
Hom.:
0
Cov.:
32
AF XY:
0.00159
AC XY:
118
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.000530
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00188
Gnomad4 NFE
AF:
0.00306
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00283
Hom.:
1
Bravo
AF:
0.00178

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesOct 17, 2023- -
Likely benign, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsJun 01, 2017- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJan 26, 2016This 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. -
Epilepsy, childhood absence, susceptibility to, 1;C2677087:Epilepsy, childhood absence, susceptibility to, 5 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 19, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.16
DANN
Benign
0.25

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.

Other links and lift over

dbSNP: rs75015217; hg19: chr15-26825446; API