chr16-23836262-G-A

Position:

• chr16-23836262-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002738.7(PRKCB):​c.87G>A​(p.Lys29Lys) variant causes a synonymous change. The variant allele was found at a frequency of 0.0068 in 1,603,234 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0070 (51 hom.)
• Consequence: PRKCB NM_002738.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.98

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]

PRKCB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 16-23836262-G-A is Benign according to our data. Variant chr16-23836262-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 735257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23836262-G-A is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd4 at 680 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.87G>A	p.Lys29Lys	synonymous_variant	1/17	ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.87G>A	p.Lys29Lys	synonymous_variant	1/17		NP_997700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.87G>A	p.Lys29Lys	synonymous_variant	1/17		NM_002738.7	ENSP00000496129.1
PRKCB	ENST00000321728.12	c.87G>A	p.Lys29Lys	synonymous_variant	1/17	1		ENSP00000318315.7
PRKCB	ENST00000498058.1	n.181G>A		non_coding_transcript_exon_variant	1/2	3
PRKCB	ENST00000645517.1	n.34G>A		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes AF: 0.00447 AC: 680 AN: 151990 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00237

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00726

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00397 AC: 945 AN: 238264 Hom.: 4 AF XY: 0.00412 AC XY: 534 AN XY: 129738

Gnomad AFR exome AF: 0.00127

Gnomad AMR exome AF: 0.00259

Gnomad ASJ exome AF: 0.000417

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00116

Gnomad FIN exome AF: 0.00292

Gnomad NFE exome AF: 0.00666

Gnomad OTH exome AF: 0.00450

GnomAD4 exome AF: 0.00704 AC: 10214 AN: 1451138 Hom.: 51 Cov.: 33 AF XY: 0.00684 AC XY: 4939 AN XY: 722144

Gnomad4 AFR exome AF: 0.00116

Gnomad4 AMR exome AF: 0.00266

Gnomad4 ASJ exome AF: 0.000273

Gnomad4 EAS exome AF: 0.0000788

Gnomad4 SAS exome AF: 0.00101

Gnomad4 FIN exome AF: 0.00304

Gnomad4 NFE exome AF: 0.00850

Gnomad4 OTH exome AF: 0.00616

GnomAD4 genome AF: 0.00447 AC: 680 AN: 152096 Hom.: 5 Cov.: 33 AF XY: 0.00422 AC XY: 314 AN XY: 74358

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.00523

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00237

Gnomad4 NFE AF: 0.00726

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00591 Hom.: 5

Bravo AF: 0.00431

Asia WGS AF: 0.000289 AC: 1 AN: 3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2023	PRKCB: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.81

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: rs146177740; hg19: chr16-23847583;