rs424741

Variant names:

• chr16-24220128-C-T
• rs424741
• NM_002738.7:c.*5312C>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.*5312C>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 0.0123 in 1,613,768 control chromosomes in the GnomAD database, including 462 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 0.033 (218 hom., cov: 32)
  • Exomes 𝑓: 0.010 (244 hom.)
• Consequence: PRKCB NM_002738.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.909
• Publications: 6 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=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.*5312C>T		3_prime_UTR_variant	Exon 17 of 17	ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.*15C>T		3_prime_UTR_variant	Exon 17 of 17		NP_997700.1
PRKCB	XM_047434365.1	c.*5312C>T		3_prime_UTR_variant	Exon 16 of 16		XP_047290321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.*5312C>T		3_prime_UTR_variant	Exon 17 of 17		NM_002738.7	ENSP00000496129.1

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4971 AN: 152106 Hom.: 217 Cov.: 32

Gnomad AFR AF: 0.0967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0177

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00701

Gnomad OTH AF: 0.0292

GnomAD2 exomes AF: 0.0145 AC: 3648 AN: 250798 AF XY: 0.0135

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.00949

Gnomad ASJ exome AF: 0.0156

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.000557

Gnomad NFE exome AF: 0.00734

Gnomad OTH exome AF: 0.0103

GnomAD4 exome AF: 0.0102 AC: 14838 AN: 1461544 Hom.: 244 Cov.: 33 AF XY: 0.0101 AC XY: 7346 AN XY: 727064

African (AFR) AF: 0.105 AC: 3529 AN: 33460

American (AMR) AF: 0.0105 AC: 470 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0172 AC: 449 AN: 26124

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39692

South Asian (SAS) AF: 0.0173 AC: 1496 AN: 86240

European-Finnish (FIN) AF: 0.000862 AC: 46 AN: 53350

Middle Eastern (MID) AF: 0.0288 AC: 166 AN: 5766

European-Non Finnish (NFE) AF: 0.00703 AC: 7818 AN: 1111806

Other (OTH) AF: 0.0143 AC: 862 AN: 60388

GnomAD4 genome AF: 0.0328 AC: 4989 AN: 152224 Hom.: 218 Cov.: 32 AF XY: 0.0315 AC XY: 2346 AN XY: 74430

African (AFR) AF: 0.0970 AC: 4027 AN: 41524

American (AMR) AF: 0.0176 AC: 269 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0168 AC: 81 AN: 4808

European-Finnish (FIN) AF: 0.000566 AC: 6 AN: 10604

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00700 AC: 476 AN: 68020

Other (OTH) AF: 0.0289 AC: 61 AN: 2114

Alfa AF: 0.0161 Hom.: 101

Bravo AF: 0.0378

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs424741; hg19: chr16-24231449;