rs191106606
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_015192.4(PLCB1):c.121A>G(p.Ile41Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000194 in 1,545,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
PLCB1
NM_015192.4 missense
NM_015192.4 missense
Scores
1
16
Clinical Significance
Conservation
PhyloP100: 4.56
Genes affected
PLCB1 (HGNC:15917): (phospholipase C beta 1) The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals. This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, PLCB1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.04039401).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCB1 | NM_015192.4 | c.121A>G | p.Ile41Val | missense_variant | 2/32 | ENST00000338037.11 | |
PLCB1 | NM_182734.3 | c.121A>G | p.Ile41Val | missense_variant | 2/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCB1 | ENST00000338037.11 | c.121A>G | p.Ile41Val | missense_variant | 2/32 | 1 | NM_015192.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152108Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000827 AC: 2AN: 241818Hom.: 0 AF XY: 0.0000152 AC XY: 2AN XY: 131148
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GnomAD4 exome AF: 0.00000144 AC: 2AN: 1393256Hom.: 0 Cov.: 22 AF XY: 0.00000144 AC XY: 1AN XY: 696778
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74436
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 20, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with PLCB1-related conditions. This variant is present in population databases (rs191106606, ExAC 0.02%). This sequence change replaces isoleucine with valine at codon 41 of the PLCB1 protein (p.Ile41Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.;N
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;N;N
REVEL
Benign
Sift
Benign
T;T;.;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
B;B;.;.;B
Vest4
MVP
MPC
0.084
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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