rs11867591

chr17-66594833-A-T

Variant summary

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

The NM_002737.3(PRKCA):c.289-46522A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 152,244 control chromosomes in the GnomAD database, including 203 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 0.043 (203 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCA	NM_002737.3	c.289-46522A>T		intron_variant		ENST00000413366.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCA	ENST00000413366.8	c.289-46522A>T		intron_variant		1	NM_002737.3	P1
PRKCA	ENST00000578063.5	c.289-46522A>T		intron_variant, NMD_transcript_variant		1
PRKCA	ENST00000284384.6	c.341+40254A>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0429 AC: 6533 AN: 152126 Hom.: 203 Cov.: 32

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00891

Gnomad FIN AF: 0.0607

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0660

Gnomad OTH AF: 0.0397

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

GnomAD4 genome AF: 0.0429 AC: 6532 AN: 152244 Hom.: 203 Cov.: 32 AF XY: 0.0418 AC XY: 3112 AN XY: 74438

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.0316

Gnomad4 ASJ AF: 0.0524

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00871

Gnomad4 FIN AF: 0.0607

Gnomad4 NFE AF: 0.0660

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0520 Hom.: 25

Bravo AF: 0.0394

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.1
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11867591; hg19: chr17-64590951;