rs12263737

Positions:

• chr10-94285156-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016341.4(PLCE1):​c.5035+191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,840 control chromosomes in the GnomAD database, including 7,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7846 hom., cov: 32)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0950

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 10-94285156-G-A is Benign according to our data. Variant chr10-94285156-G-A is described in ClinVar as [Benign]. Clinvar id is 1287760.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCE1	NM_016341.4	c.5035+191G>A		intron_variant		ENST00000371380.8	NP_057425.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8	c.5035+191G>A		intron_variant		1	NM_016341.4	ENSP00000360431.2

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47774 AN: 151722 Hom.: 7826 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.315 AC: 47826 AN: 151840 Hom.: 7846 Cov.: 32 AF XY: 0.308 AC XY: 22883 AN XY: 74210

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.333

Alfa AF: 0.304 Hom.: 6784

Bravo AF: 0.321

Asia WGS AF: 0.281 AC: 968 AN: 3456

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs12263737; hg19: chr10-96044913;