10-94227556-C-T

Variant names:

• chr10-94227556-C-T
• rs11187825
• NM_016341.4:c.1955+105C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016341.4(PLCE1):​c.1955+105C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,030,542 control chromosomes in the GnomAD database, including 210,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31790 hom., cov: 32)
  • Exomes 𝑓: 0.63 (178878 hom.)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0430
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-94227556-C-T is Benign according to our data. Variant chr10-94227556-C-T is described in ClinVar as Benign. ClinVar VariationId is 1269258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCE1	NM_016341.4	c.1955+105C>T		intron_variant	Intron 5 of 32	ENST00000371380.8	NP_057425.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8	c.1955+105C>T		intron_variant	Intron 5 of 32	1	NM_016341.4	ENSP00000360431.2

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97806 AN: 151922 Hom.: 31758 Cov.: 32

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.646

GnomAD4 exome AF: 0.632 AC: 555291 AN: 878502 Hom.: 178878 AF XY: 0.637 AC XY: 293472 AN XY: 460896

African (AFR) AF: 0.675 AC: 15060 AN: 22306

American (AMR) AF: 0.614 AC: 26935 AN: 43856

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 16389 AN: 22460

East Asian (EAS) AF: 0.919 AC: 33947 AN: 36922

South Asian (SAS) AF: 0.717 AC: 52865 AN: 73688

European-Finnish (FIN) AF: 0.566 AC: 29941 AN: 52870

Middle Eastern (MID) AF: 0.720 AC: 2844 AN: 3950

European-Non Finnish (NFE) AF: 0.604 AC: 350828 AN: 581244

Other (OTH) AF: 0.643 AC: 26482 AN: 41206

GnomAD4 genome AF: 0.644 AC: 97890 AN: 152040 Hom.: 31790 Cov.: 32 AF XY: 0.645 AC XY: 47911 AN XY: 74306

African (AFR) AF: 0.673 AC: 27894 AN: 41450

American (AMR) AF: 0.603 AC: 9216 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2562 AN: 3464

East Asian (EAS) AF: 0.926 AC: 4780 AN: 5162

South Asian (SAS) AF: 0.738 AC: 3556 AN: 4816

European-Finnish (FIN) AF: 0.572 AC: 6041 AN: 10552

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41683 AN: 67988

Other (OTH) AF: 0.649 AC: 1370 AN: 2112

Alfa AF: 0.630 Hom.: 51782

Bravo AF: 0.650

Asia WGS AF: 0.837 AC: 2910 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.58
PhyloP100		-0.043
PromoterAI		0.0094	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11187825; hg19: chr10-95987313;