chr20-478662-C-G

Position:

• chr20-478662-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_177559.3(CSNK2A1):​c.*5299G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 432,328 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 31)
  • Exomes 𝑓: 0.0019 (1 hom.)
• Consequence: CSNK2A1 NM_177559.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.44

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 20-478662-C-G is Benign according to our data. Variant chr20-478662-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2498872.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00155 (235/151658) while in subpopulation NFE AF= 0.00274 (186/67960). AF 95% confidence interval is 0.00241. There are 0 homozygotes in gnomad4. There are 119 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 235 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSNK2A1	NM_177559.3	c.*5299G>C		3_prime_UTR_variant	14/14	ENST00000217244.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSNK2A1	ENST00000217244.9	c.*5299G>C		3_prime_UTR_variant	14/14	1	NM_177559.3	P1

Frequencies

GnomAD3 genomes AF: 0.00155 AC: 235 AN: 151544 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000705

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000922

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00274

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00110 AC: 114 AN: 103468 Hom.: 0 AF XY: 0.00112 AC XY: 65 AN XY: 57792

Gnomad AFR exome AF: 0.000801

Gnomad AMR exome AF: 0.000570

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000975

Gnomad FIN exome AF: 0.000422

Gnomad NFE exome AF: 0.00254

Gnomad OTH exome AF: 0.000940

GnomAD4 exome AF: 0.00187 AC: 524 AN: 280670 Hom.: 1 Cov.: 0 AF XY: 0.00166 AC XY: 268 AN XY: 161696

Gnomad4 AFR exome AF: 0.000631

Gnomad4 AMR exome AF: 0.000743

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000138

Gnomad4 FIN exome AF: 0.000419

Gnomad4 NFE exome AF: 0.00313

Gnomad4 OTH exome AF: 0.00168

GnomAD4 genome AF: 0.00155 AC: 235 AN: 151658 Hom.: 0 Cov.: 31 AF XY: 0.00161 AC XY: 119 AN XY: 74082

Gnomad4 AFR AF: 0.000703

Gnomad4 AMR AF: 0.000921

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00274

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00143 Hom.: 0

Bravo AF: 0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

CSNK2A1: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.76
DANN	Benign	0.24

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs573587694; hg19: chr20-459306;