rs1555790846

chr20-8790220-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP2 PP5

The NM_015192.4(PLCB1):c.3382C>T(p.His1128Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLCB1 NM_015192.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.94

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, PLCB1
• PP5: Variant 20-8790220-C-T is Pathogenic according to our data. Variant chr20-8790220-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 433139.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCB1	NM_015192.4	c.3382C>T	p.His1128Tyr	missense_variant	31/32	ENST00000338037.11
PLCB1	NM_182734.3	c.3382C>T	p.His1128Tyr	missense_variant	31/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCB1	ENST00000338037.11	c.3382C>T	p.His1128Tyr	missense_variant	31/32	1	NM_015192.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Childhood epilepsy with centrotemporal spikes Pathogenic:1

Pathogenic, no assertion criteria provided

case-control

Bioinformatics Core, Luxembourg Center for Systems Biomedicine

Jan 01, 2017

CAADphred>15 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
Cadd	Uncertain	24
Dann	Uncertain	0.99
Eigen	Benign	0.0053
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D;.;D;D;D;D;D;D
M_CAP	Benign	0.0064	T
MetaRNN	Uncertain	0.48	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.83	D
Polyphen		0.0070, 0.012	.;B;B;B;.;.;.;.
Vest4		0.71, 0.70, 0.72
MutPred		0.59		.;Gain of phosphorylation at H1128 (P = 0.0502);Gain of phosphorylation at H1128 (P = 0.0502);Gain of phosphorylation at H1128 (P = 0.0502);.;.;.;.;
MVP		0.50
MPC		0.37
ClinPred		0.83	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.28

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

Other links and lift over

dbSNP: rs1555790846; hg19: chr20-8770867;