16-24035540-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_002738.7(PRKCB):c.522T>C(p.Ile174=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 1,597,342 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (7 hom., cov: 31)
  • Exomes 𝑓: 0.0032 (58 hom.)
• Consequence: PRKCB NM_002738.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-24035540-T-C is Benign according to our data. Variant chr16-24035540-T-C is described in ClinVar as [Benign]. Clinvar id is 779163.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-24035540-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.63 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00644 (972/150846) while in subpopulation SAS AF= 0.0212 (100/4724). AF 95% confidence interval is 0.0178. There are 7 homozygotes in gnomad4. There are 474 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 964 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCB	NM_002738.7	c.522T>C	p.Ile174=	synonymous_variant	5/17	ENST00000643927.1
PRKCB	NM_212535.3	c.522T>C	p.Ile174=	synonymous_variant	5/17
PRKCB	XM_047434365.1	c.135T>C	p.Ile45=	synonymous_variant	4/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCB	ENST00000643927.1	c.522T>C	p.Ile174=	synonymous_variant	5/17		NM_002738.7	A1

Frequencies

GnomAD3 genomes AF: 0.00640 AC: 964 AN: 150726 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.00221

Gnomad AMR AF: 0.00277

Gnomad ASJ AF: 0.00320

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0216

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.00820

GnomAD3 exomes AF: 0.00498 AC: 1247 AN: 250206 Hom.: 17 AF XY: 0.00605 AC XY: 819 AN XY: 135300

Gnomad AFR exome AF: 0.0156

Gnomad AMR exome AF: 0.00218

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.0223

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00170

Gnomad OTH exome AF: 0.00426

GnomAD4 exome AF: 0.00324 AC: 4692 AN: 1446496 Hom.: 58 Cov.: 33 AF XY: 0.00388 AC XY: 2793 AN XY: 719742

Gnomad4 AFR exome AF: 0.0173

Gnomad4 AMR exome AF: 0.00235

Gnomad4 ASJ exome AF: 0.00235

Gnomad4 EAS exome AF: 0.0000263

Gnomad4 SAS exome AF: 0.0225

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00151

Gnomad4 OTH exome AF: 0.00450

GnomAD4 genome AF: 0.00644 AC: 972 AN: 150846 Hom.: 7 Cov.: 31 AF XY: 0.00643 AC XY: 474 AN XY: 73684

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.00277

Gnomad4 ASJ AF: 0.00320

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0212

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00154

Gnomad4 OTH AF: 0.00812

Alfa AF: 0.00427 Hom.: 4

Bravo AF: 0.00646

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.00267

EpiControl AF: 0.00315

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.8
Dann	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs116345778; hg19: chr16-24046861;