10-94284739-G-A

Position:

• chr10-94284739-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016341.4(PLCE1):​c.4918-109G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 745,676 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (17 hom., cov: 32)
  • Exomes 𝑓: 0.012 (58 hom.)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.77

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:45193): (PLCE1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-94284739-G-A is Benign according to our data. Variant chr10-94284739-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1211753.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-94284739-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0113 (1719/152208) while in subpopulation NFE AF= 0.0176 (1198/68002). AF 95% confidence interval is 0.0168. There are 17 homozygotes in gnomad4. There are 740 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCE1	NM_016341.4	c.4918-109G>A		intron_variant		ENST00000371380.8	NP_057425.3
PLCE1-AS1	NR_033969.1	n.231-1253C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8	c.4918-109G>A		intron_variant		1	NM_016341.4	ENSP00000360431	P1
PLCE1-AS1	ENST00000425267.8	n.208-1253C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1720 AN: 152090 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.00560

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.00715

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00895

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0176

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.0123 AC: 7276 AN: 593468 Hom.: 58 AF XY: 0.0118 AC XY: 3780 AN XY: 321132

Gnomad4 AFR exome AF: 0.00536

Gnomad4 AMR exome AF: 0.00934

Gnomad4 ASJ exome AF: 0.00469

Gnomad4 EAS exome AF: 0.0000287

Gnomad4 SAS exome AF: 0.00263

Gnomad4 FIN exome AF: 0.0108

Gnomad4 NFE exome AF: 0.0169

Gnomad4 OTH exome AF: 0.0117

GnomAD4 genome AF: 0.0113 AC: 1719 AN: 152208 Hom.: 17 Cov.: 32 AF XY: 0.00995 AC XY: 740 AN XY: 74406

Gnomad4 AFR AF: 0.00558

Gnomad4 AMR AF: 0.00707

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00895

Gnomad4 NFE AF: 0.0176

Gnomad4 OTH AF: 0.0119

Alfa AF: 0.0134 Hom.: 4

Bravo AF: 0.0116

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 06, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.8
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs41291136; hg19: chr10-96044496;