20-483960-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.663

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 20-483960-G-A is Benign according to our data. Variant chr20-483960-G-A is described in ClinVar as [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 229 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSNK2A1	NM_177559.3	c.*1C>T		3_prime_UTR_variant	14/14	ENST00000217244.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSNK2A1	ENST00000217244.9	c.*1C>T		3_prime_UTR_variant	14/14	1	NM_177559.3	P1

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 229 AN: 152246 Hom.: 0 Cov.: 32

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

GnomAD3 exomes AF: 0.00140 AC: 346 AN: 247942 Hom.: 0 AF XY: 0.00149 AC XY: 200 AN XY: 134208

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 SAS exome AF: 0.00102

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.: 0 Cov.: 30 AF XY: 0.00156 AC XY: 1133 AN XY: 725396

Gnomad4 AFR exome AF: 0.000301

Gnomad4 AMR exome AF: 0.00167

Gnomad4 ASJ exome AF: 0.000961

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000909

Gnomad4 FIN exome AF: 0.000300

Gnomad4 NFE exome AF: 0.00179

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00150 AC: 229 AN: 152364 Hom.: 0 Cov.: 32 AF XY: 0.00160 AC XY: 119 AN XY: 74510

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00215

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00174 Hom.: 0

Bravo AF: 0.00152

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00218

EpiControl AF: 0.00262

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	CSNK2A1: BS1 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 14, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	6.0
Dann	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs142680688; hg19: chr20-464604;