20-8722377-G-C

Variant names:

• chr20-8722377-G-C
• rs764250569
• NM_015192.4:c.1537G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015192.4(PLCB1):​c.1537G>C​(p.Asp513His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLCB1 NM_015192.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.06

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41711697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.1537G>C	p.Asp513His	missense_variant	Exon 15 of 32	ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3	c.1537G>C	p.Asp513His	missense_variant	Exon 15 of 33		NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.1537G>C	p.Asp513His	missense_variant	Exon 15 of 32	1	NM_015192.4	ENSP00000338185.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.70	.;.;.;D;.;T;.;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.95	D;D;.;D;D;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.42	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.5	.;.;L;L;L;.;.;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.0	.;.;D;D;D;.;.;.
REVEL	Benign	0.23
Sift	Benign	0.045	.;.;D;D;D;.;.;.
Sift4G	Uncertain	0.040	.;D;D;D;D;D;D;D
Polyphen		0.93, 0.87	.;.;P;P;P;.;.;.
Vest4		0.47, 0.49, 0.47
MutPred		0.28		.;.;Loss of stability (P = 0.0531);Loss of stability (P = 0.0531);Loss of stability (P = 0.0531);.;.;.;
MVP		0.62
MPC		2.3
ClinPred		0.96	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.39

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: rs764250569; hg19: chr20-8703024;