chr17-66447877-T-C

Variant names:

• chr17-66447877-T-C
• rs228883
• NM_002737.3:c.206-48324T>C

Variant summary

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

The NM_002737.3(PRKCA):​c.206-48324T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 152,052 control chromosomes in the GnomAD database, including 34,889 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 0.68 (34889 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• 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]

ENSG00000289587 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.206-48324T>C		intron_variant	Intron 2 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.206-48324T>C		intron_variant	Intron 2 of 16	1	NM_002737.3	ENSP00000408695.3

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102747 AN: 151934 Hom.: 34860 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.676 AC: 102831 AN: 152052 Hom.: 34889 Cov.: 32 AF XY: 0.677 AC XY: 50329 AN XY: 74326

African (AFR) AF: 0.663 AC: 27490 AN: 41478

American (AMR) AF: 0.709 AC: 10840 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2326 AN: 3470

East Asian (EAS) AF: 0.714 AC: 3676 AN: 5146

South Asian (SAS) AF: 0.537 AC: 2586 AN: 4814

European-Finnish (FIN) AF: 0.704 AC: 7439 AN: 10564

Middle Eastern (MID) AF: 0.791 AC: 231 AN: 292

European-Non Finnish (NFE) AF: 0.679 AC: 46164 AN: 67976

Other (OTH) AF: 0.712 AC: 1503 AN: 2112

Alfa AF: 0.673 Hom.: 18321

Bravo AF: 0.682

Asia WGS AF: 0.615 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.46
DANN	Benign	0.15
PhyloP100		-1.2
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: rs228883; hg19: chr17-64443995;