rs8073985

Variant names:

• chr17-66466667-G-A
• rs8073985
• NM_002737.3:c.206-29534G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-66466667-G-A
• chr17-66466667-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.206-29534G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 152,124 control chromosomes in the GnomAD database, including 1,029 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 0.064 (1029 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 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.206-29534G>A		intron	N/A	NP_002728.2	L7RSM7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	ENST00000413366.8	TSL:1 MANE Select	c.206-29534G>A		intron	N/A	ENSP00000408695.3	P17252
	PRKCA	ENST00000578063.5	TSL:1	n.206-29534G>A		intron	N/A	ENSP00000462087.1	J3KRN5
	PRKCA	ENST00000882063.1		c.206-29534G>A		intron	N/A	ENSP00000552122.1

Frequencies

GnomAD3 genomes AF: 0.0634 AC: 9643 AN: 152008 Hom.: 1016 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00100

Gnomad OTH AF: 0.0441

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

GnomAD4 genome AF: 0.0637 AC: 9696 AN: 152124 Hom.: 1029 Cov.: 32 AF XY: 0.0625 AC XY: 4648 AN XY: 74382

African (AFR) AF: 0.221 AC: 9159 AN: 41490

American (AMR) AF: 0.0224 AC: 343 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4824

European-Finnish (FIN) AF: 0.0000945 AC: 1 AN: 10578

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00100 AC: 68 AN: 67988

Other (OTH) AF: 0.0437 AC: 92 AN: 2106

Alfa AF: 0.0172 Hom.: 43

Bravo AF: 0.0732

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.50
PhyloP100		-0.12
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: rs8073985; hg19: chr17-64462785;