10-94135420-G-C

Variant names:

• chr10-94135420-G-C
• rs9663362
• NM_016341.4:c.1492+2961G>C

Variant summary

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

The NM_016341.4(PLCE1):​c.1492+2961G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,892 control chromosomes in the GnomAD database, including 25,066 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 0.56 (25066 hom., cov: 32)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• 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: 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCE1	NM_016341.4	c.1492+2961G>C		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.1492+2961G>C		intron_variant	Intron 3 of 32	1	NM_016341.4	ENSP00000360431.2

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85331 AN: 151774 Hom.: 25017 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.562 AC: 85438 AN: 151892 Hom.: 25066 Cov.: 32 AF XY: 0.569 AC XY: 42215 AN XY: 74234

African (AFR) AF: 0.716 AC: 29693 AN: 41456

American (AMR) AF: 0.571 AC: 8705 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1403 AN: 3464

East Asian (EAS) AF: 0.677 AC: 3487 AN: 5152

South Asian (SAS) AF: 0.488 AC: 2348 AN: 4814

European-Finnish (FIN) AF: 0.589 AC: 6188 AN: 10506

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.468 AC: 31821 AN: 67934

Other (OTH) AF: 0.550 AC: 1160 AN: 2108

Alfa AF: 0.533 Hom.: 2621

Bravo AF: 0.569

Asia WGS AF: 0.597 AC: 2078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.37
PhyloP100		0.010
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: rs9663362; hg19: chr10-95895177;