rs921183

Variant names:

• chr2-46063277-A-C
• rs921183
• NM_005400.3:c.1438-22931A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-46063277-A-C
• chr2-46063277-A-G
• chr2-46063277-A-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.1438-22931A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 151,526 control chromosomes in the GnomAD database, including 4,875 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 0.23 (4875 hom., cov: 30)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.937
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.1438-22931A>C		intron_variant	Intron 10 of 14	ENST00000306156.8	NP_005391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCE	ENST00000306156.8	c.1438-22931A>C		intron_variant	Intron 10 of 14	1	NM_005400.3	ENSP00000306124.3

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34487 AN: 151408 Hom.: 4873 Cov.: 30

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.228 AC: 34523 AN: 151526 Hom.: 4875 Cov.: 30 AF XY: 0.227 AC XY: 16776 AN XY: 74038

African (AFR) AF: 0.405 AC: 16678 AN: 41178

American (AMR) AF: 0.162 AC: 2469 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 663 AN: 3466

East Asian (EAS) AF: 0.142 AC: 735 AN: 5158

South Asian (SAS) AF: 0.241 AC: 1154 AN: 4780

European-Finnish (FIN) AF: 0.136 AC: 1429 AN: 10494

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10855 AN: 67910

Other (OTH) AF: 0.213 AC: 450 AN: 2114

Alfa AF: 0.191 Hom.: 6083

Bravo AF: 0.234

Asia WGS AF: 0.182 AC: 634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.9
DANN	Benign	0.75
PhyloP100		0.94
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: rs921183; hg19: chr2-46290416;