10-94186763-A-G

Variant names:

• chr10-94186763-A-G
• rs2689700
• NM_016341.4:c.1809+15267A>G

Variant summary

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

The NM_016341.4(PLCE1):​c.1809+15267A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 152,162 control chromosomes in the GnomAD database, including 51,918 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 0.82 (51918 hom., cov: 33)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCE1	NM_016341.4	c.1809+15267A>G		intron_variant	Intron 4 of 32	ENST00000371380.8	NP_057425.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8	c.1809+15267A>G		intron_variant	Intron 4 of 32	1	NM_016341.4	ENSP00000360431.2

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125401 AN: 152044 Hom.: 51873 Cov.: 33

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.832

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

GnomAD4 genome AF: 0.825 AC: 125500 AN: 152162 Hom.: 51918 Cov.: 33 AF XY: 0.825 AC XY: 61389 AN XY: 74388

African (AFR) AF: 0.795 AC: 32965 AN: 41468

American (AMR) AF: 0.852 AC: 13039 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2727 AN: 3470

East Asian (EAS) AF: 0.869 AC: 4502 AN: 5180

South Asian (SAS) AF: 0.674 AC: 3244 AN: 4816

European-Finnish (FIN) AF: 0.877 AC: 9293 AN: 10592

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 57003 AN: 68016

Other (OTH) AF: 0.827 AC: 1750 AN: 2116

Alfa AF: 0.832 Hom.: 221552

Bravo AF: 0.825

Asia WGS AF: 0.755 AC: 2627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.74
PhyloP100		0.14
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: rs2689700; hg19: chr10-95946520;