10-94140878-T-A

Variant names:

• chr10-94140878-T-A
• rs1343094
• NM_016341.4:c.1492+8419T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_016341.4(PLCE1):​c.1492+8419T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,188 control chromosomes in the GnomAD database, including 36,523 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 0.66 (36523 hom., cov: 33)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

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.1492+8419T>A		intron	N/A	NP_057425.3
	PLCE1	NM_001288989.2		c.1492+8419T>A		intron	N/A	NP_001275918.1
	PLCE1	NM_001165979.2		c.568+8419T>A		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.1492+8419T>A		intron	N/A	ENSP00000360431.2
	PLCE1	ENST00000371375.2	TSL:1	c.568+8419T>A		intron	N/A	ENSP00000360426.1
	PLCE1	ENST00000692396.1		c.1492+8419T>A		intron	N/A	ENSP00000508605.1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100569 AN: 152070 Hom.: 36516 Cov.: 33

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.661 AC: 100594 AN: 152188 Hom.: 36523 Cov.: 33 AF XY: 0.666 AC XY: 49517 AN XY: 74402

African (AFR) AF: 0.333 AC: 13822 AN: 41484

American (AMR) AF: 0.772 AC: 11814 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 2574 AN: 3472

East Asian (EAS) AF: 0.655 AC: 3392 AN: 5176

South Asian (SAS) AF: 0.670 AC: 3232 AN: 4824

European-Finnish (FIN) AF: 0.830 AC: 8798 AN: 10598

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54588 AN: 68014

Other (OTH) AF: 0.698 AC: 1478 AN: 2116

Alfa AF: 0.734 Hom.: 5384

Bravo AF: 0.643

Asia WGS AF: 0.636 AC: 2209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	17
DANN	Benign	0.81
PhyloP100		2.1
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: rs1343094; hg19: chr10-95900635;