rs2764345

Variant names:

• chr10-94166342-C-G
• rs2764345
• NM_016341.4:c.1493-4838C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-94166342-C-G
• chr10-94166342-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016341.4(PLCE1):​c.1493-4838C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,056 control chromosomes in the GnomAD database, including 38,440 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 0.69 (38440 hom., cov: 31)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558
• Publications: 2 publications found

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]

PLCE1 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCE1	NM_016341.4	c.1493-4838C>G		intron_variant	Intron 3 of 32	ENST00000371380.8	NP_057425.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8	c.1493-4838C>G		intron_variant	Intron 3 of 32	1	NM_016341.4	ENSP00000360431.2

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104996 AN: 151938 Hom.: 38423 Cov.: 31

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.691 AC: 105056 AN: 152056 Hom.: 38440 Cov.: 31 AF XY: 0.695 AC XY: 51688 AN XY: 74356

African (AFR) AF: 0.429 AC: 17767 AN: 41404

American (AMR) AF: 0.784 AC: 11978 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2535 AN: 3472

East Asian (EAS) AF: 0.688 AC: 3561 AN: 5174

South Asian (SAS) AF: 0.643 AC: 3103 AN: 4824

European-Finnish (FIN) AF: 0.860 AC: 9115 AN: 10594

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54557 AN: 67988

Other (OTH) AF: 0.714 AC: 1509 AN: 2114

Alfa AF: 0.750 Hom.: 5526

Bravo AF: 0.676

Asia WGS AF: 0.645 AC: 2246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.51
DANN	Benign	0.61
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2764345; hg19: chr10-95926099;