rs741141

Variant names:

• chr17-66551536-G-A
• rs741141
• NM_002737.3:c.288+55253G>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.288+55253G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,254 control chromosomes in the GnomAD database, including 1,686 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 0.15 (1686 hom., cov: 33)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 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.288+55253G>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.288+55253G>A		intron	N/A	ENSP00000408695.3	P17252
	PRKCA	ENST00000578063.5	TSL:1	n.288+55253G>A		intron	N/A	ENSP00000462087.1	J3KRN5
	PRKCA	ENST00000882063.1		c.288+55253G>A		intron	N/A	ENSP00000552122.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22369 AN: 152136 Hom.: 1683 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.147 AC: 22393 AN: 152254 Hom.: 1686 Cov.: 33 AF XY: 0.147 AC XY: 10973 AN XY: 74446

African (AFR) AF: 0.156 AC: 6469 AN: 41558

American (AMR) AF: 0.165 AC: 2531 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 712 AN: 3472

East Asian (EAS) AF: 0.187 AC: 965 AN: 5162

South Asian (SAS) AF: 0.135 AC: 655 AN: 4834

European-Finnish (FIN) AF: 0.150 AC: 1588 AN: 10600

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.131 AC: 8930 AN: 68012

Other (OTH) AF: 0.160 AC: 339 AN: 2114

Alfa AF: 0.140 Hom.: 2523

Bravo AF: 0.151

Asia WGS AF: 0.161 AC: 561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.73
PhyloP100		-0.39
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: rs741141; hg19: chr17-64547654;