Genetic Variant CSNK2B:p.Tyr46Tyr (chr6-31667933-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02

Publications

35 publications found

Variant links:

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]

CSNK2B Gene-Disease associations (from GenCC):

Poirier-Bienvenu neurodevelopmental syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Illumina, Labcorp Genetics (formerly Invitae), G2P
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CSNK2B links:

ENSG00000263020 (HGNC:):

ENSG00000263020 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CSNK2B	NM_001320.7 link	c.138T>C	p.Tyr46Tyr	synonymous_variant	Exon 3 of 7	ENST00000375882.7	NP_001311.3	P67870N0E4C7
CSNK2B	NM_001282385.2 link	c.138T>C	p.Tyr46Tyr	synonymous_variant	Exon 3 of 7		NP_001269314.1	P67870A0A1U9X7J2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK2B	ENST00000375882.7 link	c.138T>C	p.Tyr46Tyr	synonymous_variant	Exon 3 of 7	1	NM_001320.7	ENSP00000365042.3		P67870
ENSG00000263020	ENST00000375880.6 link	c.138T>C	p.Tyr46Tyr	synonymous_variant	Exon 3 of 8	3		ENSP00000365040.2		Q5SRQ3

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41924

AN:

151962

Hom.:

6418

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.245

AC:

53681

AN:

218950

AF XY:

0.233

show subpopulations

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 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.:

AF XY:

0.199

AC XY:

140708

AN XY:

707072

show subpopulations

African (AFR)

AF:

0.397

AC:

12418

AN:

31254

American (AMR)

AF:

0.356

AC:

12638

AN:

35524

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

5500

AN:

24458

East Asian (EAS)

AF:

0.368

AC:

14255

AN:

38732

South Asian (SAS)

AF:

0.175

AC:

13963

AN:

79758

European-Finnish (FIN)

AF:

0.319

AC:

16823

AN:

52804

Middle Eastern (MID)

AF:

0.271

AC:

1519

AN:

5606

European-Non Finnish (NFE)

AF:

0.180

AC:

197081

AN:

1097376

Other (OTH)

AF:

0.221

AC:

13000

AN:

58726

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

10255

20510

30764

41019

51274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7224

14448

21672

28896

36120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.276

AC:

41981

AN:

152080

Hom.:

6432

Cov.:

AF XY:

0.282

AC XY:

20951

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.398

AC:

16511

AN:

41486

American (AMR)

AF:

0.326

AC:

4977

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

770

AN:

3472

East Asian (EAS)

AF:

0.302

AC:

1558

AN:

5154

South Asian (SAS)

AF:

0.185

AC:

892

AN:

4822

European-Finnish (FIN)

AF:

0.336

AC:

3546

AN:

10554

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.190

AC:

12914

AN:

67998

Other (OTH)

AF:

0.282

AC:

595

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1515

3030

4544

6059

7574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.219

Hom.:

17247

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

(source)

DANN

Benign

0.80

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over