rs148936543

Positions:

• chr20-8790185-C-A
• chr20-8790185-C-T

Variant summary

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

The NM_015192.4(PLCB1):​c.3347C>A​(p.Ala1116Glu) variant causes a missense change. 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLCB1 NM_015192.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 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.3347C>A	p.Ala1116Glu	missense_variant	31/32	ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3	c.3347C>A	p.Ala1116Glu	missense_variant	31/33		NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.3347C>A	p.Ala1116Glu	missense_variant	31/32	1	NM_015192.4	ENSP00000338185.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247298 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133634

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000551

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456720 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724584

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	.;.;T;.;.;T;T
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D;.;D;D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.55	D;D;D;D;D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	2.0	.;M;M;M;.;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.8	.;N;N;N;.;.;.
REVEL	Uncertain	0.31
Sift	Benign	0.55	.;T;T;T;.;.;.
Sift4G	Benign	0.88	.;T;T;T;T;T;D
Polyphen		1.0, 1.0	.;D;D;D;.;.;.
Vest4		0.69, 0.64, 0.69
MutPred		0.56		.;Gain of ubiquitination at K1119 (P = 0.0303);Gain of ubiquitination at K1119 (P = 0.0303);Gain of ubiquitination at K1119 (P = 0.0303);.;.;.;
MVP		0.48
MPC		0.68
ClinPred		0.95	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.29

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: rs148936543; hg19: chr20-8770832;