rs3729908

Positions:

• chr16-24219927-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002738.7(PRKCB):​c.*5111C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,608,562 control chromosomes in the GnomAD database, including 9,382 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 0.086 (689 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8693 hom.)
• Consequence: PRKCB NM_002738.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.*5111C>T		3_prime_UTR_variant	17/17	ENST00000643927.1	NP_002729.2
PRKCB	XM_047434365.1	c.*5111C>T		3_prime_UTR_variant	16/16		XP_047290321.1
PRKCB	NM_212535.3	c.1864-34C>T		intron_variant			NP_997700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.*5111C>T		3_prime_UTR_variant	17/17		NM_002738.7	ENSP00000496129.1
PRKCB	ENST00000321728.12	c.1864-34C>T		intron_variant		1		ENSP00000318315.7

Frequencies

GnomAD3 genomes AF: 0.0865 AC: 13148 AN: 151952 Hom.: 688 Cov.: 32

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.0760

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0920

GnomAD3 exomes AF: 0.0829 AC: 20374 AN: 245790 Hom.: 1043 AF XY: 0.0837 AC XY: 11118 AN XY: 132850

Gnomad AFR exome AF: 0.0468

Gnomad AMR exome AF: 0.0519

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.00250

Gnomad SAS exome AF: 0.0415

Gnomad FIN exome AF: 0.0738

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.105 AC: 152986 AN: 1456492 Hom.: 8693 Cov.: 34 AF XY: 0.103 AC XY: 74903 AN XY: 724074

Gnomad4 AFR exome AF: 0.0507

Gnomad4 AMR exome AF: 0.0544

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.0205

Gnomad4 SAS exome AF: 0.0404

Gnomad4 FIN exome AF: 0.0786

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.0865 AC: 13149 AN: 152070 Hom.: 689 Cov.: 32 AF XY: 0.0845 AC XY: 6286 AN XY: 74348

Gnomad4 AFR AF: 0.0541

Gnomad4 AMR AF: 0.0777

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.0103

Gnomad4 SAS AF: 0.0334

Gnomad4 FIN AF: 0.0760

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0911

Alfa AF: 0.107 Hom.: 545

Bravo AF: 0.0855

Asia WGS AF: 0.0320 AC: 112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.4
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs3729908; hg19: chr16-24231248; COSMIC: COSV105885320;