rs3886870

Variant names:

• chr2-45815339-G-A
• rs3886870
• NM_005400.3:c.349-27661G>A

Variant summary

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

The NM_005400.3(PRKCE):​c.349-27661G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,190 control chromosomes in the GnomAD database, including 3,309 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 0.19 (3309 hom., cov: 32)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 9 publications found

Genes affected

PRKCE (HGNC:9401): (protein kinase C epsilon) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This kinase has been shown to be involved in many different cellular functions, such as neuron channel activation, apoptosis, cardioprotection from ischemia, heat shock response, as well as insulin exocytosis. Knockout studies in mice suggest that this kinase is important for lipopolysaccharide (LPS)-mediated signaling in activated macrophages and may also play a role in controlling anxiety-like behavior. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.349-27661G>A		intron_variant	Intron 1 of 14	ENST00000306156.8	NP_005391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCE	ENST00000306156.8	c.349-27661G>A		intron_variant	Intron 1 of 14	1	NM_005400.3	ENSP00000306124.3

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29258 AN: 152072 Hom.: 3311 Cov.: 32

Gnomad AFR AF: 0.0592

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.192 AC: 29258 AN: 152190 Hom.: 3309 Cov.: 32 AF XY: 0.190 AC XY: 14129 AN XY: 74406

African (AFR) AF: 0.0591 AC: 2456 AN: 41552

American (AMR) AF: 0.247 AC: 3769 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 765 AN: 3462

East Asian (EAS) AF: 0.278 AC: 1441 AN: 5184

South Asian (SAS) AF: 0.235 AC: 1134 AN: 4818

European-Finnish (FIN) AF: 0.155 AC: 1636 AN: 10580

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.255 AC: 17322 AN: 67990

Other (OTH) AF: 0.221 AC: 467 AN: 2110

Alfa AF: 0.236 Hom.: 14939

Bravo AF: 0.193

Asia WGS AF: 0.210 AC: 730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.9
DANN	Benign	0.77
PhyloP100		0.27
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: rs3886870; hg19: chr2-46042478;