rs7215972

Variant names:

• chr17-66728496-G-C
• rs7215972
• NM_002737.3:c.919-4192G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-66728496-G-C
• chr17-66728496-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.919-4192G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,142 control chromosomes in the GnomAD database, including 34,524 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 0.67 (34524 hom., cov: 33)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.919-4192G>C		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.919-4192G>C		intron_variant	Intron 8 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000284384.6	n.*521-4192G>C		intron_variant	Intron 9 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102222 AN: 152024 Hom.: 34470 Cov.: 33

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.673 AC: 102336 AN: 152142 Hom.: 34524 Cov.: 33 AF XY: 0.676 AC XY: 50291 AN XY: 74362

African (AFR) AF: 0.701 AC: 29082 AN: 41492

American (AMR) AF: 0.656 AC: 10020 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2268 AN: 3468

East Asian (EAS) AF: 0.711 AC: 3681 AN: 5176

South Asian (SAS) AF: 0.654 AC: 3153 AN: 4820

European-Finnish (FIN) AF: 0.704 AC: 7452 AN: 10586

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.653 AC: 44383 AN: 67998

Other (OTH) AF: 0.661 AC: 1398 AN: 2114

Alfa AF: 0.660 Hom.: 4090

Bravo AF: 0.670

Asia WGS AF: 0.689 AC: 2398 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	1.4
DANN	Benign	0.29
PhyloP100		-0.54
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: rs7215972; hg19: chr17-64724614;