rs7084339

Variant names:

• chr10-94283975-A-G
• rs7084339
• NM_016341.4:c.4917+64A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-94283975-A-G
• chr10-94283975-A-C
• chr10-94283975-A-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.4917+64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,572,808 control chromosomes in the GnomAD database, including 75,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (8702 hom., cov: 32)
  • Exomes 𝑓: 0.30 (66648 hom.)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.783
• Publications: 10 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-AS1 (HGNC:45193): (PLCE1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-94283975-A-G is Benign according to our data. Variant chr10-94283975-A-G is described in ClinVar as Benign. ClinVar VariationId is 1235235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016341.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCE1	NM_016341.4	MANE Select	c.4917+64A>G		intron	N/A	NP_057425.3
	PLCE1	NM_001288989.2		c.4869+64A>G		intron	N/A	NP_001275918.1	B7ZM61
	PLCE1	NM_001165979.2		c.3993+64A>G		intron	N/A	NP_001159451.1	Q9P212-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCE1	ENST00000371380.8	TSL:1 MANE Select	c.4917+64A>G		intron	N/A	ENSP00000360431.2	Q9P212-1
	PLCE1	ENST00000371375.2	TSL:1	c.3993+64A>G		intron	N/A	ENSP00000360426.1	Q9P212-2
	PLCE1	ENST00000875452.1		c.4917+64A>G		intron	N/A	ENSP00000545511.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50539 AN: 151986 Hom.: 8682 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.302 AC: 429660 AN: 1420704 Hom.: 66648 AF XY: 0.304 AC XY: 214929 AN XY: 707490

African (AFR) AF: 0.435 AC: 14142 AN: 32500

American (AMR) AF: 0.183 AC: 7993 AN: 43688

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 10945 AN: 25210

East Asian (EAS) AF: 0.238 AC: 9065 AN: 38134

South Asian (SAS) AF: 0.268 AC: 22738 AN: 84866

European-Finnish (FIN) AF: 0.226 AC: 11515 AN: 50894

Middle Eastern (MID) AF: 0.437 AC: 2442 AN: 5590

European-Non Finnish (NFE) AF: 0.307 AC: 332098 AN: 1081528

Other (OTH) AF: 0.321 AC: 18722 AN: 58294

GnomAD4 genome AF: 0.333 AC: 50592 AN: 152104 Hom.: 8702 Cov.: 32 AF XY: 0.325 AC XY: 24182 AN XY: 74370

African (AFR) AF: 0.423 AC: 17535 AN: 41486

American (AMR) AF: 0.261 AC: 3986 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1563 AN: 3470

East Asian (EAS) AF: 0.229 AC: 1185 AN: 5180

South Asian (SAS) AF: 0.264 AC: 1273 AN: 4822

European-Finnish (FIN) AF: 0.210 AC: 2228 AN: 10590

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.319 AC: 21648 AN: 67968

Other (OTH) AF: 0.343 AC: 723 AN: 2108

Alfa AF: 0.269 Hom.: 1159

Bravo AF: 0.338

Asia WGS AF: 0.287 AC: 997 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.4
DANN	Benign	0.70
PhyloP100		0.78
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: rs7084339; hg19: chr10-96043732; COSMIC: COSV53342714;