chr20-8684958-C-G

Position:

• chr20-8684958-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015192.4(PLCB1):​c.889C>G​(p.Arg297Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 1.37

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.889C>G	p.Arg297Gly	missense_variant	10/32	ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3	c.889C>G	p.Arg297Gly	missense_variant	10/33		NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.889C>G	p.Arg297Gly	missense_variant	10/32	1	NM_015192.4	ENSP00000338185.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.22
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.70	.;.;.;D;.;T;.;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.80	T;T;.;T;T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.61	D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	.;.;M;M;M;.;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.0	.;.;D;D;D;.;.;.
REVEL	Benign	0.27
Sift	Benign	0.037	.;.;D;D;D;.;.;.
Sift4G	Uncertain	0.047	.;D;T;T;T;T;T;T
Polyphen		0.93, 0.082	.;.;P;B;P;.;.;.
Vest4		0.82, 0.83
MutPred		0.69		.;.;Loss of MoRF binding (P = 0.0335);Loss of MoRF binding (P = 0.0335);Loss of MoRF binding (P = 0.0335);.;.;.;
MVP		0.69
MPC		1.7
ClinPred		0.92	D
GERP RS		6.1
Varity_R		0.78
gMVP		0.72

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: rs149661663; hg19: chr20-8665605;