14-61242375-A-G

Variant names:

• chr14-61242375-A-G
• rs1959660
• ENST00000555185.5:c.-19+54707A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000555185.5(PRKCH):​c.-19+54707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 152,292 control chromosomes in the GnomAD database, including 67,312 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 0.94 (67312 hom., cov: 32)
• Consequence: PRKCH ENST00000555185.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.565

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCH	XM_024449661.2	c.-121+54707A>G		intron_variant	Intron 1 of 13		XP_024305429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCH	ENST00000555185.5	c.-19+54707A>G		intron_variant	Intron 1 of 3	3		ENSP00000451871.1
PRKCH	ENST00000556778.5	c.-57+54707A>G		intron_variant	Intron 1 of 5	4		ENSP00000452055.1
PRKCH	ENST00000557294.5	c.-109+54707A>G		intron_variant	Intron 1 of 1	4		ENSP00000452129.1

Frequencies

GnomAD3 genomes AF: 0.935 AC: 142349 AN: 152174 Hom.: 67266 Cov.: 32

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.975

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.992

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.947

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

GnomAD4 genome AF: 0.935 AC: 142451 AN: 152292 Hom.: 67312 Cov.: 32 AF XY: 0.938 AC XY: 69858 AN XY: 74474

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.975

Gnomad4 ASJ AF: 0.995

Gnomad4 EAS AF: 0.975

Gnomad4 SAS AF: 0.992

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.947

Alfa AF: 0.974 Hom.: 3478

Bravo AF: 0.927

Asia WGS AF: 0.968 AC: 3366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.88
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1959660; hg19: chr14-61709093;