NM_002738.7:c.522T>C

Variant names:

• chr16-24035540-T-C
• rs116345778
• NM_002738.7:c.522T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002738.7(PRKCB):​c.522T>C​(p.Ile174Ile) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.63
• Publications: 0 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 -21 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 VariationId is 779163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 972 AD gene.

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.522T>C	p.Ile174Ile	synonymous	Exon 5 of 17	NP_002729.2
	PRKCB	NM_212535.3		c.522T>C	p.Ile174Ile	synonymous	Exon 5 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.522T>C	p.Ile174Ile	synonymous	Exon 5 of 17	ENSP00000496129.1	P05771-2
	PRKCB	ENST00000321728.12	TSL:1	c.522T>C	p.Ile174Ile	synonymous	Exon 5 of 17	ENSP00000318315.7	P05771-1
	PRKCB	ENST00000965655.1		c.600T>C	p.Ile200Ile	synonymous	Exon 6 of 18	ENSP00000635714.1

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

GnomAD2 exomes AF: 0.00498 AC: 1247 AN: 250206 AF XY: 0.00605

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 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

African (AFR) AF: 0.0173 AC: 570 AN: 33040

American (AMR) AF: 0.00235 AC: 104 AN: 44210

Ashkenazi Jewish (ASJ) AF: 0.00235 AC: 60 AN: 25548

East Asian (EAS) AF: 0.0000263 AC: 1 AN: 38090

South Asian (SAS) AF: 0.0225 AC: 1936 AN: 86046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52256

Middle Eastern (MID) AF: 0.0156 AC: 89 AN: 5696

European-Non Finnish (NFE) AF: 0.00151 AC: 1665 AN: 1102332

Other (OTH) AF: 0.00450 AC: 267 AN: 59278

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

African (AFR) AF: 0.0167 AC: 691 AN: 41286

American (AMR) AF: 0.00277 AC: 42 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.00320 AC: 11 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 5050

South Asian (SAS) AF: 0.0212 AC: 100 AN: 4724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10282

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.00154 AC: 104 AN: 67598

Other (OTH) AF: 0.00812 AC: 17 AN: 2094

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.65
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs116345778; hg19: chr16-24046861; COSMIC: COSV107327300;