dbSNP rs142680688: CSNK2A1:c.*1C>T (chr20-483960-G-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_177559.3(CSNK2A1):c.*1C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,610,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 0 hom. )

Consequence

CSNK2A1
NM_177559.3 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.663

Publications

0 publications found

Variant links:

Genes affected

CSNK2A1 (HGNC:2457): (casein kinase 2 alpha 1) Casein kinase II is a serine/threonine protein kinase that phosphorylates acidic proteins such as casein. It is involved in various cellular processes, including cell cycle control, apoptosis, and circadian rhythm. The kinase exists as a tetramer and is composed of an alpha, an alpha-prime, and two beta subunits. The alpha subunits contain the catalytic activity while the beta subunits undergo autophosphorylation. The protein encoded by this gene represents the alpha subunit. Multiple transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Apr 2018]

CSNK2A1 Gene-Disease associations (from GenCC):

Okur-Chung neurodevelopmental syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Illumina, Labcorp Genetics (formerly Invitae)
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

CSNK2A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.021).

BP6

Variant 20-483960-G-A is Benign according to our data. Variant chr20-483960-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1264567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0015 (229/152364) while in subpopulation AMR AF = 0.0032 (49/15306). AF 95% confidence interval is 0.00249. There are 0 homozygotes in GnomAd4. There are 119 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 229 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177559.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CSNK2A1	NM_177559.3	MANE Select	c.*1C>T	3_prime_UTR	Exon 14 of 14	NP_808227.1	P68400-1
CSNK2A1	NM_001362770.2		c.*1C>T	3_prime_UTR	Exon 14 of 15	NP_001349699.1	P68400-1
CSNK2A1	NM_001362771.2		c.*1C>T	3_prime_UTR	Exon 13 of 14	NP_001349700.1	P68400-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CSNK2A1	ENST00000217244.9	TSL:1 MANE Select	c.*1C>T	3_prime_UTR	Exon 14 of 14	ENSP00000217244.3	P68400-1
CSNK2A1	ENST00000349736.10	TSL:1	c.*1C>T	3_prime_UTR	Exon 12 of 12	ENSP00000339247.6	P68400-2
CSNK2A1	ENST00000400227.8	TSL:1	c.1060+2416C>T	intron	N/A	ENSP00000383086.3	E7EU96

Frequencies

GnomAD3 genomes

AF:

0.00150

AC:

229

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00140

AC:

346

AN:

247942

AF XY:

0.00149

show subpopulations

Gnomad AFR exome

AF:

0.000192

Gnomad AMR exome

AF:

0.00178

Gnomad ASJ exome

AF:

0.00100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00205

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00157

AC:

2291

AN:

1458158

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

1133

AN XY:

725396

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000301

AC:

AN:

33212

American (AMR)

AF:

0.00167

AC:

AN:

44312

Ashkenazi Jewish (ASJ)

AF:

0.000961

AC:

AN:

26022

East Asian (EAS)

AF:

0.00

AC:

AN:

39418

South Asian (SAS)

AF:

0.000909

AC:

AN:

85804

European-Finnish (FIN)

AF:

0.000300

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00126

AC:

AN:

5536

European-Non Finnish (NFE)

AF:

0.00179

AC:

1990

AN:

1110268

Other (OTH)

AF:

0.00151

AC:

AN:

60206

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.341

Heterozygous variant carriers

141

282

422

563

704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

140

210

280

350

<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:

0.00150

AC:

229

AN:

152364

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.000385

AC:

AN:

41588

American (AMR)

AF:

0.00320

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00145

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00215

AC:

146

AN:

68040

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00120

Hom.:

Bravo

AF:

0.00152

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00218

EpiControl

AF:

0.00262

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.0

(source)

DANN

Benign

0.86

PhyloP100

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over