rs11074583

Variant names:

• chr16-23855592-G-A
• rs11074583
• NM_002738.7:c.205+18186G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-23855592-G-A
• chr16-23855592-G-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.205+18186G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,108 control chromosomes in the GnomAD database, including 21,086 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 0.51 (21086 hom., cov: 33)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.205+18186G>A		intron_variant	Intron 2 of 16	ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.205+18186G>A		intron_variant	Intron 2 of 16		NP_997700.1
PRKCB	XM_047434365.1	c.-183+15633G>A		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+18186G>A		intron_variant	Intron 2 of 16		NM_002738.7	ENSP00000496129.1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76826 AN: 151990 Hom.: 21083 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.505 AC: 76845 AN: 152108 Hom.: 21086 Cov.: 33 AF XY: 0.513 AC XY: 38141 AN XY: 74354

African (AFR) AF: 0.271 AC: 11246 AN: 41488

American (AMR) AF: 0.602 AC: 9209 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1688 AN: 3470

East Asian (EAS) AF: 0.653 AC: 3374 AN: 5166

South Asian (SAS) AF: 0.565 AC: 2724 AN: 4820

European-Finnish (FIN) AF: 0.671 AC: 7094 AN: 10576

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39659 AN: 67986

Other (OTH) AF: 0.518 AC: 1091 AN: 2108

Alfa AF: 0.556 Hom.: 38194

Bravo AF: 0.488

Asia WGS AF: 0.598 AC: 2081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.080
DANN	Benign	0.55
PhyloP100		-0.46
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: rs11074583; hg19: chr16-23866913;