16-24219927-C-T

Variant names:

• chr16-24219927-C-T
• rs3729908
• NM_002738.7:c.*5111C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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]

ENSG00000297426 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.*5111C>T		3_prime_UTR_variant	Exon 17 of 17	ENST00000643927.1	NP_002729.2
PRKCB	XM_047434365.1	c.*5111C>T		3_prime_UTR_variant	Exon 16 of 16		XP_047290321.1
PRKCB	NM_212535.3	c.1864-34C>T		intron_variant	Intron 16 of 16		NP_997700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.*5111C>T		3_prime_UTR_variant	Exon 17 of 17		NM_002738.7	ENSP00000496129.1

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

GnomAD2 exomes AF: 0.0829 AC: 20374 AN: 245790 AF XY: 0.0837

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 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

African (AFR) AF: 0.0507 AC: 1688 AN: 33298

American (AMR) AF: 0.0544 AC: 2404 AN: 44216

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4301 AN: 25980

East Asian (EAS) AF: 0.0205 AC: 808 AN: 39488

South Asian (SAS) AF: 0.0404 AC: 3459 AN: 85650

European-Finnish (FIN) AF: 0.0786 AC: 4178 AN: 53166

Middle Eastern (MID) AF: 0.117 AC: 674 AN: 5742

European-Non Finnish (NFE) AF: 0.117 AC: 129298 AN: 1108782

Other (OTH) AF: 0.103 AC: 6176 AN: 60170

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

African (AFR) AF: 0.0541 AC: 2242 AN: 41478

American (AMR) AF: 0.0777 AC: 1186 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 573 AN: 3464

East Asian (EAS) AF: 0.0103 AC: 53 AN: 5170

South Asian (SAS) AF: 0.0334 AC: 161 AN: 4820

European-Finnish (FIN) AF: 0.0760 AC: 804 AN: 10576

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7673 AN: 67984

Other (OTH) AF: 0.0911 AC: 192 AN: 2108

Alfa AF: 0.107 Hom.: 597

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
PhyloP100		-0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3729908; hg19: chr16-24231248; COSMIC: COSV105885320;