rs1998709

Positions:

• chr10-94124817-C-A

Variant summary

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

The NM_016341.4(PLCE1):​c.1207-7357C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,074 control chromosomes in the GnomAD database, including 8,661 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 0.33 (8661 hom., cov: 33)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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]

LOC107984255 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCE1	NM_016341.4	c.1207-7357C>A		intron_variant		ENST00000371380.8	NP_057425.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8	c.1207-7357C>A		intron_variant		1	NM_016341.4	ENSP00000360431	P1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49890 AN: 151956 Hom.: 8633 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.0810

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.328 AC: 49955 AN: 152074 Hom.: 8661 Cov.: 33 AF XY: 0.321 AC XY: 23872 AN XY: 74328

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.0806

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.348

Alfa AF: 0.359 Hom.: 5262

Bravo AF: 0.337

Asia WGS AF: 0.152 AC: 529 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	6.3
DANN	Benign	0.74

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: rs1998709; hg19: chr10-95884574;