rs4953249

Variant names:

• chr2-45765718-G-A
• rs4953249
• NM_005400.3:c.349-77282G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-45765718-G-A
• chr2-45765718-G-T

Variant summary

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

The NM_005400.3(PRKCE):​c.349-77282G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,216 control chromosomes in the GnomAD database, including 55,772 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 0.85 (55772 hom., cov: 32)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223
• Publications: 5 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.349-77282G>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.349-77282G>A		intron_variant	Intron 1 of 14	1	NM_005400.3	ENSP00000306124.3

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129688 AN: 152098 Hom.: 55743 Cov.: 32

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.915

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.853 AC: 129777 AN: 152216 Hom.: 55772 Cov.: 32 AF XY: 0.855 AC XY: 63633 AN XY: 74428

African (AFR) AF: 0.736 AC: 30568 AN: 41516

American (AMR) AF: 0.908 AC: 13896 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2998 AN: 3472

East Asian (EAS) AF: 0.965 AC: 4988 AN: 5170

South Asian (SAS) AF: 0.858 AC: 4137 AN: 4824

European-Finnish (FIN) AF: 0.881 AC: 9334 AN: 10590

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.896 AC: 60936 AN: 68024

Other (OTH) AF: 0.862 AC: 1823 AN: 2114

Alfa AF: 0.885 Hom.: 34824

Bravo AF: 0.850

Asia WGS AF: 0.884 AC: 3074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.6
DANN	Benign	0.57
PhyloP100		-0.22
Mutation Taster		=43/57	disease causing

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: rs4953249; hg19: chr2-45992857;