10-94291660-G-T

Variant names:

• chr10-94291660-G-T
• rs753724
• NM_016341.4:c.5036-1848G>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.5036-1848G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.08 in 152,136 control chromosomes in the GnomAD database, including 572 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 0.080 (572 hom., cov: 32)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.552
• Publications: 20 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: Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCE1	NM_016341.4	MANE Select	c.5036-1848G>T		intron	N/A	NP_057425.3
	PLCE1	NM_001288989.2		c.4988-1848G>T		intron	N/A	NP_001275918.1	B7ZM61
	PLCE1	NM_001165979.2		c.4112-1848G>T		intron	N/A	NP_001159451.1	Q9P212-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCE1	ENST00000371380.8	TSL:1 MANE Select	c.5036-1848G>T		intron	N/A	ENSP00000360431.2	Q9P212-1
	PLCE1	ENST00000371375.2	TSL:1	c.4112-1848G>T		intron	N/A	ENSP00000360426.1	Q9P212-2
	PLCE1	ENST00000875452.1		c.5036-1848G>T		intron	N/A	ENSP00000545511.1

Frequencies

GnomAD3 genomes AF: 0.0800 AC: 12162 AN: 152018 Hom.: 572 Cov.: 32

Gnomad AFR AF: 0.0435

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.0821

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.0453

Gnomad FIN AF: 0.0334

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0974

Gnomad OTH AF: 0.0957

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

GnomAD4 genome AF: 0.0800 AC: 12164 AN: 152136 Hom.: 572 Cov.: 32 AF XY: 0.0756 AC XY: 5626 AN XY: 74374

African (AFR) AF: 0.0436 AC: 1808 AN: 41504

American (AMR) AF: 0.0820 AC: 1252 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3472

East Asian (EAS) AF: 0.188 AC: 972 AN: 5174

South Asian (SAS) AF: 0.0451 AC: 217 AN: 4808

European-Finnish (FIN) AF: 0.0334 AC: 354 AN: 10606

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0974 AC: 6624 AN: 67990

Other (OTH) AF: 0.0947 AC: 200 AN: 2112

Alfa AF: 0.0760 Hom.: 301

Bravo AF: 0.0836

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.041
DANN	Benign	0.56
PhyloP100		-0.55
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: rs753724; hg19: chr10-96051417;