NM_002738.7:c.1770C>T

Variant names:

• chr16-24191137-C-T
• rs3729904
• NM_002738.7:c.1770C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_002738.7(PRKCB):​c.1770C>T​(p.Gly590Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,613,202 control chromosomes in the GnomAD database, including 50,312 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 0.25 (5032 hom., cov: 31)
  • Exomes 𝑓: 0.24 (45280 hom.)
• Consequence: PRKCB NM_002738.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 20 publications found

Genes affected

PRKCB (HGNC:9395): (protein kinase C beta) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and 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 protein kinase has been reported to be involved in many different cellular functions, such as B cell activation, apoptosis induction, endothelial cell proliferation, and intestinal sugar absorption. Studies in mice also suggest that this kinase may also regulate neuronal functions and correlate fear-induced conflict behavior after stress. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=-1.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002738.7. 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
	PRKCB	NM_002738.7	MANE Select	c.1770C>T	p.Gly590Gly	synonymous	Exon 16 of 17	NP_002729.2
	PRKCB	NM_212535.3		c.1770C>T	p.Gly590Gly	synonymous	Exon 16 of 17	NP_997700.1	P05771-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCB	ENST00000643927.1	MANE Select	c.1770C>T	p.Gly590Gly	synonymous	Exon 16 of 17	ENSP00000496129.1	P05771-2
	PRKCB	ENST00000321728.12	TSL:1	c.1770C>T	p.Gly590Gly	synonymous	Exon 16 of 17	ENSP00000318315.7	P05771-1
	PRKCB	ENST00000965655.1		c.1848C>T	p.Gly616Gly	synonymous	Exon 17 of 18	ENSP00000635714.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38148 AN: 151794 Hom.: 5027 Cov.: 31

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.0951

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.267

GnomAD2 exomes AF: 0.232 AC: 58240 AN: 251222 AF XY: 0.240

Gnomad AFR exome AF: 0.302

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.279

Gnomad EAS exome AF: 0.0881

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.259

GnomAD4 exome AF: 0.245 AC: 357680 AN: 1461290 Hom.: 45280 Cov.: 33 AF XY: 0.248 AC XY: 180419 AN XY: 726978

African (AFR) AF: 0.300 AC: 10037 AN: 33464

American (AMR) AF: 0.155 AC: 6918 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 7136 AN: 26130

East Asian (EAS) AF: 0.109 AC: 4321 AN: 39686

South Asian (SAS) AF: 0.335 AC: 28865 AN: 86192

European-Finnish (FIN) AF: 0.193 AC: 10299 AN: 53410

Middle Eastern (MID) AF: 0.323 AC: 1864 AN: 5768

European-Non Finnish (NFE) AF: 0.246 AC: 273322 AN: 1111572

Other (OTH) AF: 0.247 AC: 14918 AN: 60360

GnomAD4 genome AF: 0.251 AC: 38181 AN: 151912 Hom.: 5032 Cov.: 31 AF XY: 0.249 AC XY: 18482 AN XY: 74240

African (AFR) AF: 0.303 AC: 12541 AN: 41398

American (AMR) AF: 0.215 AC: 3270 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3472

East Asian (EAS) AF: 0.0951 AC: 492 AN: 5172

South Asian (SAS) AF: 0.338 AC: 1622 AN: 4802

European-Finnish (FIN) AF: 0.186 AC: 1964 AN: 10552

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16438 AN: 67966

Other (OTH) AF: 0.266 AC: 560 AN: 2108

Alfa AF: 0.231 Hom.: 3055

Bravo AF: 0.250

Asia WGS AF: 0.226 AC: 789 AN: 3478

EpiCase AF: 0.248

EpiControl AF: 0.249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.1
DANN	Benign	0.65
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs3729904; hg19: chr16-24202458; COSMIC: COSV57769668;