rs1998709

Variant names:

• chr10-94124817-C-A
• rs1998709
• NM_016341.4:c.1207-7357C>A

Variant summary

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

The NM_016341.4(PLCE1):​c.1207-7357C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,074 control chromosomes in the GnomAD database, including 8,661 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 0.33 (8661 hom., cov: 33)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 3 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

LOC107984255 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.373 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.1207-7357C>A		intron	N/A	NP_057425.3
	PLCE1	NM_001288989.2		c.1207-7357C>A		intron	N/A	NP_001275918.1	B7ZM61
	PLCE1	NM_001165979.2		c.283-7357C>A		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.1207-7357C>A		intron	N/A	ENSP00000360431.2	Q9P212-1
	PLCE1	ENST00000371375.2	TSL:1	c.283-7357C>A		intron	N/A	ENSP00000360426.1	Q9P212-2
	PLCE1	ENST00000875452.1		c.1207-7357C>A		intron	N/A	ENSP00000545511.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49890 AN: 151956 Hom.: 8633 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.0810

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.328 AC: 49955 AN: 152074 Hom.: 8661 Cov.: 33 AF XY: 0.321 AC XY: 23872 AN XY: 74328

African (AFR) AF: 0.281 AC: 11666 AN: 41478

American (AMR) AF: 0.374 AC: 5718 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3470

East Asian (EAS) AF: 0.0806 AC: 417 AN: 5174

South Asian (SAS) AF: 0.209 AC: 1010 AN: 4822

European-Finnish (FIN) AF: 0.292 AC: 3077 AN: 10552

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25605 AN: 67984

Other (OTH) AF: 0.348 AC: 736 AN: 2116

Alfa AF: 0.360 Hom.: 5771

Bravo AF: 0.337

Asia WGS AF: 0.152 AC: 529 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	6.3
DANN	Benign	0.74
PhyloP100		1.0
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: rs1998709; hg19: chr10-95884574;