rs2764343

chr10-94148264-A-Cchr10-94148264-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016341.4(PLCE1):c.1492+15805A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 152,236 control chromosomes in the GnomAD database, including 64,075 homozygotes. 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: 𝑓 0.91 (64075 hom., cov: 32)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

Genes affected

PLCE1 (HGNC:17175): (phospholipase C epsilon 1) This gene encodes a phospholipase enzyme that catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate to generate two second messengers: inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). These second messengers subsequently regulate various processes affecting cell growth, differentiation, and gene expression. This enzyme is regulated by small monomeric GTPases of the Ras and Rho families and by heterotrimeric G proteins. In addition to its phospholipase C catalytic activity, this enzyme has an N-terminal domain with guanine nucleotide exchange (GEF) activity. Mutations in this gene cause early-onset nephrotic syndrome; characterized by proteinuria, edema, and diffuse mesangial sclerosis or focal and segmental glomerulosclerosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCE1	NM_016341.4	c.1492+15805A>C		intron_variant		ENST00000371380.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCE1	ENST00000371380.8	c.1492+15805A>C		intron_variant		1	NM_016341.4	P1

Frequencies

GnomAD3 genomes AF: 0.914 AC: 138962 AN: 152118 Hom.: 64036 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.981

Gnomad FIN AF: 0.984

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.932

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.913 AC: 139059 AN: 152236 Hom.: 64075 Cov.: 32 AF XY: 0.916 AC XY: 68170 AN XY: 74432

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.948

Gnomad4 ASJ AF: 0.970

Gnomad4 EAS AF: 0.888

Gnomad4 SAS AF: 0.981

Gnomad4 FIN AF: 0.984

Gnomad4 NFE AF: 0.972

Gnomad4 OTH AF: 0.932

Alfa AF: 0.957 Hom.: 29360

Bravo AF: 0.904

Asia WGS AF: 0.935 AC: 3249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.2
Dann	Benign	0.70

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: rs2764343; hg19: chr10-95908021;