10-94100172-A-G

Variant names:

• chr10-94100172-A-G
• rs4918082
• ENST00000432782.2:n.1098T>C

Variant summary

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

The ENST00000371380.8(PLCE1):​c.1207-32002A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,982 control chromosomes in the GnomAD database, including 12,244 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 0.38 (12244 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLCE1 ENST00000371380.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278
• Publications: 8 publications found

Genes affected

PLCE1-AS2 (HGNC:51206): (PLCE1 antisense RNA 2)

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371380.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCE1	NM_016341.4	MANE Select	c.1207-32002A>G		intron	N/A	NP_057425.3
	PLCE1-AS2	NR_120615.1		n.1097T>C		non_coding_transcript_exon	Exon 3 of 3
	PLCE1	NM_001288989.2		c.1207-32002A>G		intron	N/A	NP_001275918.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCE1-AS2	ENST00000432782.2	TSL:1	n.1098T>C		non_coding_transcript_exon	Exon 3 of 3
	PLCE1	ENST00000371380.8	TSL:1 MANE Select	c.1207-32002A>G		intron	N/A	ENSP00000360431.2
	PLCE1	ENST00000371375.2	TSL:1	c.282+10796A>G		intron	N/A	ENSP00000360426.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58024 AN: 151864 Hom.: 12211 Cov.: 31

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.418

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.382 AC: 58101 AN: 151982 Hom.: 12244 Cov.: 31 AF XY: 0.381 AC XY: 28334 AN XY: 74300

African (AFR) AF: 0.537 AC: 22221 AN: 41408

American (AMR) AF: 0.449 AC: 6865 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1312 AN: 3470

East Asian (EAS) AF: 0.548 AC: 2825 AN: 5154

South Asian (SAS) AF: 0.292 AC: 1405 AN: 4816

European-Finnish (FIN) AF: 0.245 AC: 2595 AN: 10592

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.289 AC: 19627 AN: 67954

Other (OTH) AF: 0.415 AC: 873 AN: 2106

Alfa AF: 0.326 Hom.: 19243

Bravo AF: 0.409

Asia WGS AF: 0.403 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.74
DANN	Benign	0.49
PhyloP100		-0.28
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: rs4918082; hg19: chr10-95859929;