chr15-26547873-T-C
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2BP6_Very_StrongBS2
The NM_000814.6(GABRB3):c.1342A>G(p.Ile448Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,614,102 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. I448I) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
GABRB3
NM_000814.6 missense
NM_000814.6 missense
Scores
2
8
3
Clinical Significance
Conservation
PhyloP100: 7.90
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 -11 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, GABRB3
BP6
?
Variant 15-26547873-T-C is Benign according to our data. Variant chr15-26547873-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 696921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAdExome at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRB3 | NM_000814.6 | c.1342A>G | p.Ile448Val | missense_variant | 9/9 | ENST00000311550.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRB3 | ENST00000311550.10 | c.1342A>G | p.Ile448Val | missense_variant | 9/9 | 1 | NM_000814.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152228Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250694Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135510
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461874Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727236
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74368
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Epilepsy, childhood absence, susceptibility to, 1;C2677087:Epilepsy, childhood absence, susceptibility to, 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 03, 2020 | See Variant Classification Assertion Criteria. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T;T;T;.;.;T;T
Polyphen
0.72, 0.81, 0.67
.;P;.;P;P;.;.;.;.
Vest4
MVP
MPC
1.8
ClinPred
T
GERP RS
Varity_R
gMVP
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