14-61490240-C-G

Variant names:

• chr14-61490240-C-G
• rs4902067
• NM_006255.5:c.1433+4584C>G

Variant summary

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

The NM_006255.5(PRKCH):​c.1433+4584C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,108 control chromosomes in the GnomAD database, including 39,520 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 0.69 (39520 hom., cov: 32)
• Consequence: PRKCH NM_006255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426
• Publications: 2 publications found

Genes affected

PRKCH (HGNC:9403): (protein kinase C eta) 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. It is a calcium-independent and phospholipids-dependent protein kinase. It is predominantly expressed in epithelial tissues and has been shown to reside specifically in the cell nucleus. This protein kinase can regulate keratinocyte differentiation by activating the MAP kinase MAPK13 (p38delta)-activated protein kinase cascade that targets CCAAT/enhancer-binding protein alpha (CEBPA). It is also found to mediate the transcription activation of the transglutaminase 1 (TGM1) gene. Mutations in this gene are associated with susceptibility to cerebral infarction. [provided by RefSeq, Sep 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCH	NM_006255.5	c.1433+4584C>G		intron_variant	Intron 10 of 13	ENST00000332981.11	NP_006246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCH	ENST00000332981.11	c.1433+4584C>G		intron_variant	Intron 10 of 13	1	NM_006255.5	ENSP00000329127.5

Frequencies

GnomAD3 genomes AF: 0.691 AC: 105014 AN: 151990 Hom.: 39514 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.691 AC: 105050 AN: 152108 Hom.: 39520 Cov.: 32 AF XY: 0.689 AC XY: 51244 AN XY: 74334

African (AFR) AF: 0.374 AC: 15495 AN: 41444

American (AMR) AF: 0.754 AC: 11518 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3173 AN: 3470

East Asian (EAS) AF: 0.503 AC: 2603 AN: 5178

South Asian (SAS) AF: 0.731 AC: 3525 AN: 4822

European-Finnish (FIN) AF: 0.809 AC: 8548 AN: 10572

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57550 AN: 68018

Other (OTH) AF: 0.726 AC: 1537 AN: 2116

Alfa AF: 0.688 Hom.: 2419

Bravo AF: 0.675

Asia WGS AF: 0.607 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.21
DANN	Benign	0.45
PhyloP100		-0.43
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: rs4902067; hg19: chr14-61956958;