rs759117

Variant names:

• chr17-66705505-G-A
• rs759117
• NM_002737.3:c.918+16458G>A

Variant summary

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

The NM_002737.3(PRKCA):​c.918+16458G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,108 control chromosomes in the GnomAD database, including 28,724 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 0.61 (28724 hom., cov: 33)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 7 publications found

Genes affected

PRKCA (HGNC:9393): (protein kinase C alpha) 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 reported to play roles in many different cellular processes, such as cell adhesion, cell transformation, cell cycle checkpoint, and cell volume control. Knockout studies in mice suggest that this kinase may be a fundamental regulator of cardiac contractility and Ca(2+) handling in myocytes. [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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.918+16458G>A		intron_variant	Intron 8 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.918+16458G>A		intron_variant	Intron 8 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000284384.6	n.*520+16458G>A		intron_variant	Intron 9 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93255 AN: 151990 Hom.: 28683 Cov.: 33

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.614 AC: 93348 AN: 152108 Hom.: 28724 Cov.: 33 AF XY: 0.615 AC XY: 45772 AN XY: 74370

African (AFR) AF: 0.658 AC: 27310 AN: 41494

American (AMR) AF: 0.585 AC: 8933 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2239 AN: 3468

East Asian (EAS) AF: 0.554 AC: 2862 AN: 5168

South Asian (SAS) AF: 0.571 AC: 2755 AN: 4824

European-Finnish (FIN) AF: 0.651 AC: 6890 AN: 10578

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40302 AN: 67978

Other (OTH) AF: 0.596 AC: 1259 AN: 2112

Alfa AF: 0.598 Hom.: 4303

Bravo AF: 0.610

Asia WGS AF: 0.568 AC: 1972 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	0.73
DANN	Benign	0.69
PhyloP100		-0.054
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs759117; hg19: chr17-64701623;