rs721429

Variant names:

• chr17-66695787-G-A
• rs721429
• NM_002737.3:c.918+6740G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-66695787-G-A
• chr17-66695787-G-C
• chr17-66695787-G-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.918+6740G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,960 control chromosomes in the GnomAD database, including 18,025 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 0.48 (18025 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.918+6740G>A		intron_variant	Intron 8 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.918+6740G>A		intron_variant	Intron 8 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000578063.5	n.919-640G>A		intron_variant	Intron 8 of 9	1		ENSP00000462087.1
PRKCA	ENST00000284384.6	n.*520+6740G>A		intron_variant	Intron 9 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73156 AN: 151842 Hom.: 17992 Cov.: 32

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.482 AC: 73245 AN: 151960 Hom.: 18025 Cov.: 32 AF XY: 0.481 AC XY: 35731 AN XY: 74264

African (AFR) AF: 0.566 AC: 23421 AN: 41416

American (AMR) AF: 0.437 AC: 6669 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1614 AN: 3470

East Asian (EAS) AF: 0.498 AC: 2573 AN: 5168

South Asian (SAS) AF: 0.390 AC: 1877 AN: 4816

European-Finnish (FIN) AF: 0.491 AC: 5172 AN: 10542

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30281 AN: 67968

Other (OTH) AF: 0.452 AC: 952 AN: 2108

Alfa AF: 0.453 Hom.: 50048

Bravo AF: 0.482

Asia WGS AF: 0.435 AC: 1514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0070
DANN	Benign	0.69
PhyloP100		-1.8
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: rs721429; hg19: chr17-64691905;