17-66791776-A-G

Variant names:

• chr17-66791776-A-G
• rs4791037
• NM_002737.3:c.1854+2797A>G

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+2797A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,222 control chromosomes in the GnomAD database, including 2,341 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 (2341 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.95
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	NM_002737.3	MANE Select	c.1854+2797A>G		intron	N/A	NP_002728.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	ENST00000413366.8	TSL:1 MANE Select	c.1854+2797A>G		intron	N/A	ENSP00000408695.3
	PRKCA	ENST00000882063.1		c.1854+2797A>G		intron	N/A	ENSP00000552122.1
	PRKCA	ENST00000960436.1		c.1746+2797A>G		intron	N/A	ENSP00000630495.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19607 AN: 152104 Hom.: 2331 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.0553

Gnomad FIN AF: 0.0281

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0464

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.129 AC: 19654 AN: 152222 Hom.: 2341 Cov.: 32 AF XY: 0.127 AC XY: 9471 AN XY: 74446

African (AFR) AF: 0.310 AC: 12887 AN: 41506

American (AMR) AF: 0.109 AC: 1671 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0479 AC: 166 AN: 3468

East Asian (EAS) AF: 0.181 AC: 935 AN: 5172

South Asian (SAS) AF: 0.0547 AC: 264 AN: 4826

European-Finnish (FIN) AF: 0.0281 AC: 298 AN: 10616

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0464 AC: 3154 AN: 68024

Other (OTH) AF: 0.110 AC: 233 AN: 2112

Alfa AF: 0.0792 Hom.: 416

Bravo AF: 0.144

Asia WGS AF: 0.129 AC: 448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0010
DANN	Benign	0.20
PhyloP100		-6.0
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: rs4791037; hg19: chr17-64787894;