17-66497757-A-T

Variant names:

• chr17-66497757-A-T
• rs228875
• NM_002737.3:c.288+1474A>T

Variant summary

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

The NM_002737.3(PRKCA):​c.288+1474A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 152,040 control chromosomes in the GnomAD database, including 34,887 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 0.67 (34887 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.288+1474A>T		intron_variant	Intron 3 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.288+1474A>T		intron_variant	Intron 3 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000578063.5	n.288+1474A>T		intron_variant	Intron 3 of 9	1		ENSP00000462087.1
PRKCA	ENST00000284384.6	n.279+1474A>T		intron_variant	Intron 3 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102465 AN: 151922 Hom.: 34851 Cov.: 32

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.675 AC: 102559 AN: 152040 Hom.: 34887 Cov.: 32 AF XY: 0.674 AC XY: 50054 AN XY: 74304

African (AFR) AF: 0.739 AC: 30619 AN: 41458

American (AMR) AF: 0.699 AC: 10681 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2251 AN: 3466

East Asian (EAS) AF: 0.542 AC: 2793 AN: 5154

South Asian (SAS) AF: 0.481 AC: 2323 AN: 4826

European-Finnish (FIN) AF: 0.680 AC: 7189 AN: 10566

Middle Eastern (MID) AF: 0.757 AC: 221 AN: 292

European-Non Finnish (NFE) AF: 0.654 AC: 44456 AN: 67978

Other (OTH) AF: 0.696 AC: 1468 AN: 2108

Alfa AF: 0.671 Hom.: 4279

Bravo AF: 0.683

Asia WGS AF: 0.529 AC: 1840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.79
DANN	Benign	0.71
PhyloP100		-0.61
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: rs228875; hg19: chr17-64493875; COSMIC: COSV52583874;