dbSNP rs9267531: CSNK2B:c.292-132A>G (chr6-31668965-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001320.7(CSNK2B):c.292-132A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 675,906 control chromosomes in the GnomAD database, including 2,999 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.073 ( 536 hom., cov: 32)

Exomes 𝑓: 0.079 ( 2463 hom. )

Consequence

CSNK2B
NM_001320.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.23

Publications

41 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-31668965-A-G is Benign according to our data. Variant chr6-31668965-A-G is described in ClinVar as Benign. ClinVar VariationId is 1182177.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK2B	NM_001320.7 link	c.292-132A>G		intron_variant	Intron 4 of 6	ENST00000375882.7	NP_001311.3	P67870N0E4C7
CSNK2B	NM_001282385.2 link	c.292-132A>G		intron_variant	Intron 4 of 6		NP_001269314.1	P67870A0A1U9X7J2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK2B	ENST00000375882.7 link	c.292-132A>G		intron_variant	Intron 4 of 6	1	NM_001320.7	ENSP00000365042.3		P67870
ENSG00000263020	ENST00000375880.6 link	c.292-132A>G		intron_variant	Intron 4 of 7	3		ENSP00000365040.2		Q5SRQ3

Frequencies

GnomAD3 genomes

AF:

0.0731

AC:

11122

AN:

152156

Hom.:

536

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0504

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0354

Gnomad ASJ

AF:

0.0398

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0789

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0560

GnomAD4 exome

AF:

0.0791

AC:

41426

AN:

523632

Hom.:

2463

Cov.:

AF XY:

0.0755

AC XY:

20851

AN XY:

276028

show subpopulations

African (AFR)

AF:

0.0525

AC:

744

AN:

14174

American (AMR)

AF:

0.0264

AC:

634

AN:

23990

Ashkenazi Jewish (ASJ)

AF:

0.0421

AC:

636

AN:

15104

East Asian (EAS)

AF:

0.0000620

AC:

AN:

32258

South Asian (SAS)

AF:

0.00264

AC:

137

AN:

51936

European-Finnish (FIN)

AF:

0.0813

AC:

3383

AN:

41626

Middle Eastern (MID)

AF:

0.00765

AC:

AN:

2744

European-Non Finnish (NFE)

AF:

0.107

AC:

33635

AN:

313272

Other (OTH)

AF:

0.0783

AC:

2234

AN:

28528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2027

4053

6080

8106

10133

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

312

624

936

1248

1560

<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:

0.0730

AC:

11122

AN:

152274

Hom.:

536

Cov.:

AF XY:

0.0681

AC XY:

5074

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0503

AC:

2090

AN:

41552

American (AMR)

AF:

0.0353

AC:

540

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0398

AC:

138

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00145

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0789

AC:

837

AN:

10610

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7323

AN:

68002

Other (OTH)

AF:

0.0554

AC:

117

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

512

1024

1536

2048

2560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.106

Hom.:

2847

Bravo

AF:

0.0694

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 11, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.031

(source)

DANN

Benign

0.61

PhyloP100

-2.2

PromoterAI

-0.0060

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over