rs935673

Variant names:

• chr2-45895218-A-G
• rs935673
• NM_005400.3:c.412+52155A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-45895218-A-G
• chr2-45895218-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.412+52155A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,680 control chromosomes in the GnomAD database, including 9,783 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 0.35 (9783 hom., cov: 32)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005400.3. 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
	PRKCE	NM_005400.3	MANE Select	c.412+52155A>G		intron	N/A	NP_005391.1	Q02156

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCE	ENST00000306156.8	TSL:1 MANE Select	c.412+52155A>G		intron	N/A	ENSP00000306124.3	Q02156
	PRKCE	ENST00000872579.1		c.412+52155A>G		intron	N/A	ENSP00000542638.1
	PRKCE	ENST00000476675.5	TSL:4	n.314+52155A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53221 AN: 151564 Hom.: 9780 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.351 AC: 53257 AN: 151680 Hom.: 9783 Cov.: 32 AF XY: 0.355 AC XY: 26312 AN XY: 74094

African (AFR) AF: 0.370 AC: 15286 AN: 41288

American (AMR) AF: 0.378 AC: 5772 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1034 AN: 3464

East Asian (EAS) AF: 0.573 AC: 2958 AN: 5160

South Asian (SAS) AF: 0.534 AC: 2572 AN: 4818

European-Finnish (FIN) AF: 0.304 AC: 3195 AN: 10508

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21264 AN: 67878

Other (OTH) AF: 0.357 AC: 753 AN: 2112

Alfa AF: 0.336 Hom.: 1363

Bravo AF: 0.358

Asia WGS AF: 0.529 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.9
DANN	Benign	0.26
PhyloP100		1.1
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: rs935673; hg19: chr2-46122357;