rs8074995

Variant names:

• chr17-66796013-G-A
• rs8074995
• NM_002737.3:c.1854+7034G>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.1854+7034G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,196 control chromosomes in the GnomAD database, including 1,401 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 0.13 (1401 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453
• Publications: 15 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002737.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	NM_002737.3	MANE Select	c.1854+7034G>A		intron	N/A	NP_002728.2	L7RSM7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	ENST00000413366.8	TSL:1 MANE Select	c.1854+7034G>A		intron	N/A	ENSP00000408695.3	P17252
	PRKCA	ENST00000882063.1		c.1855-435G>A		intron	N/A	ENSP00000552122.1
	PRKCA	ENST00000960436.1		c.1746+7034G>A		intron	N/A	ENSP00000630495.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19923 AN: 152078 Hom.: 1399 Cov.: 32

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0688

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.131 AC: 19936 AN: 152196 Hom.: 1401 Cov.: 32 AF XY: 0.133 AC XY: 9873 AN XY: 74410

African (AFR) AF: 0.0892 AC: 3703 AN: 41518

American (AMR) AF: 0.146 AC: 2237 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 374 AN: 3470

East Asian (EAS) AF: 0.177 AC: 913 AN: 5168

South Asian (SAS) AF: 0.0691 AC: 333 AN: 4822

European-Finnish (FIN) AF: 0.189 AC: 1997 AN: 10582

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9877 AN: 68022

Other (OTH) AF: 0.130 AC: 275 AN: 2114

Alfa AF: 0.139 Hom.: 5996

Bravo AF: 0.126

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.67
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8074995; hg19: chr17-64792131;