chr17-66567402-A-G

Variant names:

• chr17-66567402-A-G
• rs7220007
• NM_002737.3:c.288+71119A>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.288+71119A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,740 control chromosomes in the GnomAD database, including 28,555 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 0.60 (28555 hom., cov: 29)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.288+71119A>G		intron_variant	Intron 3 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.288+71119A>G		intron_variant	Intron 3 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000578063.5	n.288+71119A>G		intron_variant	Intron 3 of 9	1		ENSP00000462087.1
PRKCA	ENST00000284384.6	n.340+12823A>G		intron_variant	Intron 4 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90824 AN: 151620 Hom.: 28509 Cov.: 29

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.599 AC: 90935 AN: 151740 Hom.: 28555 Cov.: 29 AF XY: 0.600 AC XY: 44473 AN XY: 74126

African (AFR) AF: 0.800 AC: 33104 AN: 41376

American (AMR) AF: 0.599 AC: 9134 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2155 AN: 3470

East Asian (EAS) AF: 0.507 AC: 2591 AN: 5106

South Asian (SAS) AF: 0.643 AC: 3073 AN: 4780

European-Finnish (FIN) AF: 0.479 AC: 5046 AN: 10532

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.501 AC: 34013 AN: 67906

Other (OTH) AF: 0.598 AC: 1261 AN: 2110

Alfa AF: 0.533 Hom.: 93907

Bravo AF: 0.615

Asia WGS AF: 0.604 AC: 2102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.53
PhyloP100		-0.48
Mutation Taster		=99/1	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: rs7220007; hg19: chr17-64563520;