rs1989647

Variant names:

• chr16-23948099-G-A
• rs1989647
• NM_002738.7:c.206-40409G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-23948099-G-A
• chr16-23948099-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.206-40409G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,718 control chromosomes in the GnomAD database, including 9,809 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 0.35 (9809 hom., cov: 30)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.670
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCB	NM_002738.7	MANE Select	c.206-40409G>A		intron	N/A	NP_002729.2
	PRKCB	NM_212535.3		c.206-40409G>A		intron	N/A	NP_997700.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCB	ENST00000643927.1	MANE Select	c.206-40409G>A		intron	N/A	ENSP00000496129.1
	PRKCB	ENST00000321728.12	TSL:1	c.206-40409G>A		intron	N/A	ENSP00000318315.7
	PRKCB	ENST00000965655.1		c.284-40409G>A		intron	N/A	ENSP00000635714.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53811 AN: 151600 Hom.: 9796 Cov.: 30

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.355 AC: 53856 AN: 151718 Hom.: 9809 Cov.: 30 AF XY: 0.357 AC XY: 26483 AN XY: 74086

African (AFR) AF: 0.366 AC: 15127 AN: 41354

American (AMR) AF: 0.311 AC: 4743 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1673 AN: 3468

East Asian (EAS) AF: 0.344 AC: 1769 AN: 5136

South Asian (SAS) AF: 0.518 AC: 2487 AN: 4798

European-Finnish (FIN) AF: 0.324 AC: 3407 AN: 10510

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23333 AN: 67886

Other (OTH) AF: 0.369 AC: 775 AN: 2102

Alfa AF: 0.352 Hom.: 41370

Bravo AF: 0.355

Asia WGS AF: 0.377 AC: 1312 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.47
PhyloP100		0.67
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: rs1989647; hg19: chr16-23959420;