rs4561502

Variant names:

• chr17-66400862-C-A
• rs4561502
• NM_002737.3:c.205+94735C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-66400862-C-A
• chr17-66400862-C-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.205+94735C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,030 control chromosomes in the GnomAD database, including 26,221 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 0.58 (26221 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• 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]

PRKCA-AS1 (HGNC:51347): (PRKCA antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.647 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.205+94735C>A		intron	N/A	NP_002728.2	L7RSM7
	PRKCA-AS1	NR_110822.1		n.1207-2644G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	ENST00000413366.8	TSL:1 MANE Select	c.205+94735C>A		intron	N/A	ENSP00000408695.3	P17252
	PRKCA	ENST00000578063.5	TSL:1	n.205+94735C>A		intron	N/A	ENSP00000462087.1	J3KRN5
	PRKCA	ENST00000882063.1		c.205+94735C>A		intron	N/A	ENSP00000552122.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88395 AN: 151912 Hom.: 26203 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.582 AC: 88456 AN: 152030 Hom.: 26221 Cov.: 32 AF XY: 0.581 AC XY: 43154 AN XY: 74320

African (AFR) AF: 0.475 AC: 19704 AN: 41464

American (AMR) AF: 0.540 AC: 8244 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2402 AN: 3472

East Asian (EAS) AF: 0.460 AC: 2370 AN: 5156

South Asian (SAS) AF: 0.638 AC: 3080 AN: 4824

European-Finnish (FIN) AF: 0.610 AC: 6445 AN: 10572

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44307 AN: 67956

Other (OTH) AF: 0.601 AC: 1269 AN: 2112

Alfa AF: 0.622 Hom.: 13590

Bravo AF: 0.568

Asia WGS AF: 0.503 AC: 1752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.37
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs4561502; hg19: chr17-64396980;