rs75914945
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_000814.6(GABRB3):c.1293G>A(p.Arg431=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000601 in 1,614,196 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00062 ( 1 hom. )
Consequence
GABRB3
NM_000814.6 synonymous
NM_000814.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.14
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
Variant 15-26547922-C-T is Benign according to our data. Variant chr15-26547922-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 386386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.14 with no splicing effect.
BS2
?
High AC in GnomAd4 at 70 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRB3 | NM_000814.6 | c.1293G>A | p.Arg431= | synonymous_variant | 9/9 | ENST00000311550.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRB3 | ENST00000311550.10 | c.1293G>A | p.Arg431= | synonymous_variant | 9/9 | 1 | NM_000814.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000460 AC: 70AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000521 AC: 131AN: 251316Hom.: 0 AF XY: 0.000582 AC XY: 79AN XY: 135838
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GnomAD4 exome AF: 0.000616 AC: 900AN: 1461888Hom.: 1 Cov.: 31 AF XY: 0.000619 AC XY: 450AN XY: 727246
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GnomAD4 genome ? AF: 0.000460 AC: 70AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24AN XY: 74482
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 09, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | GABRB3: BP4, BS1 - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 16, 2017 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 26, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Epilepsy, childhood absence, susceptibility to, 1;C2677087:Epilepsy, childhood absence, susceptibility to, 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at