14-61441614-G-T

Variant names:

• chr14-61441614-G-T
• rs1957895
• NM_006255.5:c.428-1497G>T

Variant summary

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

The NM_006255.5(PRKCH):​c.428-1497G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 151,982 control chromosomes in the GnomAD database, including 45,940 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 0.74 (45940 hom., cov: 31)
• Consequence: PRKCH NM_006255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 17 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=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCH	NM_006255.5	c.428-1497G>T		intron_variant	Intron 2 of 13	ENST00000332981.11	NP_006246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCH	ENST00000332981.11	c.428-1497G>T		intron_variant	Intron 2 of 13	1	NM_006255.5	ENSP00000329127.5

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111803 AN: 151866 Hom.: 45935 Cov.: 31

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.736 AC: 111833 AN: 151982 Hom.: 45940 Cov.: 31 AF XY: 0.741 AC XY: 55074 AN XY: 74326

African (AFR) AF: 0.344 AC: 14241 AN: 41348

American (AMR) AF: 0.863 AC: 13190 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3165 AN: 3470

East Asian (EAS) AF: 0.604 AC: 3128 AN: 5178

South Asian (SAS) AF: 0.860 AC: 4151 AN: 4828

European-Finnish (FIN) AF: 0.901 AC: 9525 AN: 10572

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.908 AC: 61728 AN: 67992

Other (OTH) AF: 0.769 AC: 1620 AN: 2106

Alfa AF: 0.851 Hom.: 171896

Bravo AF: 0.718

Asia WGS AF: 0.705 AC: 2455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.0
DANN	Benign	0.86
PhyloP100		-0.021
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: rs1957895; hg19: chr14-61908332;