17-66607456-C-T

Variant names:

• chr17-66607456-C-T
• rs2361491
• NM_002737.3:c.289-33899C>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.289-33899C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,048 control chromosomes in the GnomAD database, including 11,948 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 0.38 (11948 hom., cov: 33)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 3 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 = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.289-33899C>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.289-33899C>T		intron_variant	Intron 3 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000578063.5	n.289-33899C>T		intron_variant	Intron 3 of 9	1		ENSP00000462087.1
PRKCA	ENST00000284384.6	n.341-33899C>T		intron_variant	Intron 4 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58371 AN: 151930 Hom.: 11922 Cov.: 33

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.384 AC: 58455 AN: 152048 Hom.: 11948 Cov.: 33 AF XY: 0.383 AC XY: 28422 AN XY: 74290

African (AFR) AF: 0.507 AC: 21018 AN: 41460

American (AMR) AF: 0.398 AC: 6081 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1470 AN: 3470

East Asian (EAS) AF: 0.252 AC: 1304 AN: 5176

South Asian (SAS) AF: 0.443 AC: 2137 AN: 4824

European-Finnish (FIN) AF: 0.271 AC: 2857 AN: 10548

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22369 AN: 67972

Other (OTH) AF: 0.394 AC: 830 AN: 2106

Alfa AF: 0.333 Hom.: 8187

Bravo AF: 0.396

Asia WGS AF: 0.367 AC: 1277 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.65
PhyloP100		0.019
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: rs2361491; hg19: chr17-64603574;