rs7404928

Variant names:

• chr16-23877519-T-C
• rs7404928
• NM_002738.7:c.205+40113T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-23877519-T-C
• chr16-23877519-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002738.7(PRKCB):​c.205+40113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,042 control chromosomes in the GnomAD database, including 4,185 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 0.21 (4185 hom., cov: 31)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 25 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.205+40113T>C		intron_variant	Intron 2 of 16	ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.205+40113T>C		intron_variant	Intron 2 of 16		NP_997700.1
PRKCB	XM_047434365.1	c.-183+37560T>C		intron_variant	Intron 1 of 15		XP_047290321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.205+40113T>C		intron_variant	Intron 2 of 16		NM_002738.7	ENSP00000496129.1
PRKCB	ENST00000321728.12	c.205+40113T>C		intron_variant	Intron 2 of 16	1		ENSP00000318315.7
PRKCB	ENST00000498739.1	c.-27+40113T>C		intron_variant	Intron 1 of 3	4		ENSP00000459227.1
PRKCB	ENST00000645517.1	n.153-15445T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32549 AN: 151924 Hom.: 4183 Cov.: 31

Gnomad AFR AF: 0.0938

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.238

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.214 AC: 32551 AN: 152042 Hom.: 4185 Cov.: 31 AF XY: 0.216 AC XY: 16026 AN XY: 74330

African (AFR) AF: 0.0937 AC: 3888 AN: 41486

American (AMR) AF: 0.195 AC: 2984 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1298 AN: 3462

East Asian (EAS) AF: 0.361 AC: 1863 AN: 5160

South Asian (SAS) AF: 0.445 AC: 2135 AN: 4800

European-Finnish (FIN) AF: 0.210 AC: 2226 AN: 10586

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17289 AN: 67958

Other (OTH) AF: 0.234 AC: 495 AN: 2112

Alfa AF: 0.249 Hom.: 22770

Bravo AF: 0.211

Asia WGS AF: 0.342 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.47
PhyloP100		-1.6
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: rs7404928; hg19: chr16-23888840;