rs2764343

Variant names:

• chr10-94148264-A-C
• rs2764343
• NM_016341.4:c.1492+15805A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-94148264-A-C
• chr10-94148264-A-G
• chr10-94148264-A-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.1492+15805A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 152,236 control chromosomes in the GnomAD database, including 64,075 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 0.91 (64075 hom., cov: 32)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCE1	NM_016341.4	c.1492+15805A>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+15805A>C		intron_variant	Intron 3 of 32	1	NM_016341.4	ENSP00000360431.2

Frequencies

GnomAD3 genomes AF: 0.914 AC: 138962 AN: 152118 Hom.: 64036 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.981

Gnomad FIN AF: 0.984

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.932

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

GnomAD4 genome AF: 0.913 AC: 139059 AN: 152236 Hom.: 64075 Cov.: 32 AF XY: 0.916 AC XY: 68170 AN XY: 74432

African (AFR) AF: 0.775 AC: 32186 AN: 41512

American (AMR) AF: 0.948 AC: 14493 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 3369 AN: 3472

East Asian (EAS) AF: 0.888 AC: 4586 AN: 5166

South Asian (SAS) AF: 0.981 AC: 4730 AN: 4822

European-Finnish (FIN) AF: 0.984 AC: 10459 AN: 10624

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.972 AC: 66101 AN: 68028

Other (OTH) AF: 0.932 AC: 1971 AN: 2114

Alfa AF: 0.958 Hom.: 32983

Bravo AF: 0.904

Asia WGS AF: 0.935 AC: 3249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.70
PhyloP100		-1.3
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: rs2764343; hg19: chr10-95908021;