20-484151-G-A

Variant names:

• chr20-484151-G-A
• rs114285156
• NM_177559.3:c.1061-75C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_177559.3(CSNK2A1):​c.1061-75C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,202,486 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00058 (7 hom.)
• Consequence: CSNK2A1 NM_177559.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.328
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-484151-G-A is Benign according to our data. Variant chr20-484151-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1186946.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00692 (1054/152328) while in subpopulation AFR AF = 0.0239 (993/41572). AF 95% confidence interval is 0.0227. There are 12 homozygotes in GnomAd4. There are 475 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1054 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK2A1	NM_177559.3	MANE Select	c.1061-75C>T		intron	N/A	NP_808227.1	P68400-1
	CSNK2A1	NM_001362770.2		c.1061-75C>T		intron	N/A	NP_001349699.1	P68400-1
	CSNK2A1	NM_001362771.2		c.1061-75C>T		intron	N/A	NP_001349700.1	P68400-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK2A1	ENST00000217244.9	TSL:1 MANE Select	c.1061-75C>T		intron	N/A	ENSP00000217244.3	P68400-1
	CSNK2A1	ENST00000400227.8	TSL:1	c.1060+2225C>T		intron	N/A	ENSP00000383086.3	E7EU96
	CSNK2A1	ENST00000349736.10	TSL:1	c.653-75C>T		intron	N/A	ENSP00000339247.6	P68400-2

Frequencies

GnomAD3 genomes AF: 0.00692 AC: 1053 AN: 152210 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00525

GnomAD4 exome AF: 0.000576 AC: 605 AN: 1050158 Hom.: 7 AF XY: 0.000543 AC XY: 281 AN XY: 517832

African (AFR) AF: 0.0230 AC: 496 AN: 21548

American (AMR) AF: 0.00172 AC: 29 AN: 16826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16956

East Asian (EAS) AF: 0.0000351 AC: 1 AN: 28500

South Asian (SAS) AF: 0.0000370 AC: 2 AN: 54094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44996

Middle Eastern (MID) AF: 0.00106 AC: 5 AN: 4726

European-Non Finnish (NFE) AF: 0.0000208 AC: 17 AN: 818002

Other (OTH) AF: 0.00124 AC: 55 AN: 44510

GnomAD4 genome AF: 0.00692 AC: 1054 AN: 152328 Hom.: 12 Cov.: 32 AF XY: 0.00638 AC XY: 475 AN XY: 74486

African (AFR) AF: 0.0239 AC: 993 AN: 41572

American (AMR) AF: 0.00281 AC: 43 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68036

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.00638 Hom.: 0

Bravo AF: 0.00808

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.40
DANN	Benign	0.41
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs114285156; hg19: chr20-464795;