10-94298879-G-T

Variant names:

• chr10-94298879-G-T
• rs117607728
• NM_016341.4:c.5458+210G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_016341.4(PLCE1):​c.5458+210G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00334 in 152,292 control chromosomes in the GnomAD database, including 1 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 0.0033 (1 hom., cov: 32)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 5 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00334 (508/152292) while in subpopulation NFE AF = 0.00604 (411/68020). AF 95% confidence interval is 0.00556. There are 1 homozygotes in GnomAd4. There are 243 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016341.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCE1	NM_016341.4	MANE Select	c.5458+210G>T		intron	N/A	NP_057425.3
	PLCE1	NM_001288989.2		c.5410+210G>T		intron	N/A	NP_001275918.1
	PLCE1	NM_001165979.2		c.4534+210G>T		intron	N/A	NP_001159451.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCE1	ENST00000371380.8	TSL:1 MANE Select	c.5458+210G>T		intron	N/A	ENSP00000360431.2
	PLCE1	ENST00000371375.2	TSL:1	c.4534+210G>T		intron	N/A	ENSP00000360426.1
	PLCE1	ENST00000692396.1		c.5410+210G>T		intron	N/A	ENSP00000508605.1

Frequencies

GnomAD3 genomes AF: 0.00334 AC: 508 AN: 152174 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00604

Gnomad OTH AF: 0.000478

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

GnomAD4 genome AF: 0.00334 AC: 508 AN: 152292 Hom.: 1 Cov.: 32 AF XY: 0.00326 AC XY: 243 AN XY: 74464

African (AFR) AF: 0.00108 AC: 45 AN: 41548

American (AMR) AF: 0.00105 AC: 16 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00236 AC: 25 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00604 AC: 411 AN: 68020

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00326 Hom.: 0

Bravo AF: 0.00321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.87
DANN	Benign	0.51
PhyloP100		-0.044
Mutation Taster		=100/0	polymorphism

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: rs117607728; hg19: chr10-96058636;