rs377053037
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_015192.4(PLCB1):c.2405C>T(p.Thr802Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000578 in 1,558,152 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000057 ( 0 hom. )
Consequence
PLCB1
NM_015192.4 missense
NM_015192.4 missense
Scores
2
6
5
Clinical Significance
Conservation
PhyloP100: 4.86
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, PLCB1
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCB1 | NM_015192.4 | c.2405C>T | p.Thr802Ile | missense_variant | 22/32 | ENST00000338037.11 | |
PLCB1 | NM_182734.3 | c.2405C>T | p.Thr802Ile | missense_variant | 22/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCB1 | ENST00000338037.11 | c.2405C>T | p.Thr802Ile | missense_variant | 22/32 | 1 | NM_015192.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152150Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000903 AC: 2AN: 221478Hom.: 0 AF XY: 0.00000829 AC XY: 1AN XY: 120610
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GnomAD4 exome AF: 0.00000569 AC: 8AN: 1406002Hom.: 0 Cov.: 24 AF XY: 0.00000428 AC XY: 3AN XY: 700508
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152150Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74316
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 20, 2016 | - - |
Developmental and epileptic encephalopathy, 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 802 of the PLCB1 protein (p.Thr802Ile). This variant is present in population databases (rs377053037, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with PLCB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 436322). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
Polyphen
1.0, 0.37
.;.;D;B;D;.;.;.;.
Vest4
0.55, 0.56, 0.56
MVP
0.33
MPC
1.5
ClinPred
D
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