rs14365

Positions:

• chr6-31667933-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001320.7(CSNK2B):​c.138T>C​(p.Tyr46Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,576,318 control chromosomes in the GnomAD database, including 38,254 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 0.28 (6432 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31822 hom.)
• Consequence: CSNK2B NM_001320.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

Genes affected

CSNK2B (HGNC:2460): (casein kinase 2 beta) This gene encodes the beta subunit of casein kinase II, a ubiquitous protein kinase which regulates metabolic pathways, signal transduction, transcription, translation, and replication. The enzyme is composed of three subunits, alpha, alpha prime and beta, which form a tetrameric holoenzyme. The alpha and alpha prime subunits are catalytic, while the beta subunit serves regulatory functions. The enzyme localizes to the endoplasmic reticulum and the Golgi apparatus. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ENSG00000263020 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=1.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSNK2B	NM_001320.7	c.138T>C	p.Tyr46Tyr	synonymous_variant	3/7	ENST00000375882.7	NP_001311.3
CSNK2B	NM_001282385.2	c.138T>C	p.Tyr46Tyr	synonymous_variant	3/7		NP_001269314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSNK2B	ENST00000375882.7	c.138T>C	p.Tyr46Tyr	synonymous_variant	3/7	1	NM_001320.7	ENSP00000365042.3
ENSG00000263020	ENST00000375880.6	c.138T>C	p.Tyr46Tyr	synonymous_variant	3/8	3		ENSP00000365040.2

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41924 AN: 151962 Hom.: 6418 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.282

GnomAD3 exomes AF: 0.245 AC: 53681 AN: 218950 Hom.: 7451 AF XY: 0.233 AC XY: 27754 AN XY: 119062

Gnomad AFR exome AF: 0.403

Gnomad AMR exome AF: 0.362

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.305

Gnomad SAS exome AF: 0.178

Gnomad FIN exome AF: 0.321

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.244

GnomAD4 exome AF: 0.202 AC: 287197 AN: 1424238 Hom.: 31822 Cov.: 31 AF XY: 0.199 AC XY: 140708 AN XY: 707072

Gnomad4 AFR exome AF: 0.397

Gnomad4 AMR exome AF: 0.356

Gnomad4 ASJ exome AF: 0.225

Gnomad4 EAS exome AF: 0.368

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.276 AC: 41981 AN: 152080 Hom.: 6432 Cov.: 32 AF XY: 0.282 AC XY: 20951 AN XY: 74324

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.282

Alfa AF: 0.207 Hom.: 6645

Bravo AF: 0.284

Asia WGS AF: 0.269 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.8
DANN	Benign	0.80

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: rs14365; hg19: chr6-31635710; COSMIC: COSV63263748; COSMIC: COSV63263748;