chr20-478765-C-CAAAA

Position:

• chr20-478765-C-CAAAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000400227.8(CSNK2A1):​c.1061-6_1061-5insTTTT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 175,820 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (1 hom., cov: 27)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: CSNK2A1 ENST00000400227.8 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0680

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 -10 ACMG points.

• BP6: Variant 20-478765-C-CAAAA is Benign according to our data. Variant chr20-478765-C-CAAAA is described in ClinVar as [Likely_benign]. Clinvar id is 2652128.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000228 (26/113926) while in subpopulation AFR AF= 0.000698 (22/31502). AF 95% confidence interval is 0.000473. There are 1 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSNK2A1	NM_177559.3	c.*5195_*5196insTTTT		3_prime_UTR_variant	14/14	ENST00000217244.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSNK2A1	ENST00000217244.9	c.*5195_*5196insTTTT		3_prime_UTR_variant	14/14	1	NM_177559.3	P1

Frequencies

GnomAD3 genomes AF: 0.000219 AC: 25 AN: 113948 Hom.: 1 Cov.: 27

Gnomad AFR AF: 0.000668

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000176

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000192

Gnomad OTH AF: 0.000663

GnomAD4 exome AF: 0.000291 AC: 18 AN: 61894 Hom.: 0 Cov.: 0 AF XY: 0.000247 AC XY: 9 AN XY: 36460

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000704

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000444

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000236

Gnomad4 OTH exome AF: 0.000370

GnomAD4 genome AF: 0.000228 AC: 26 AN: 113926 Hom.: 1 Cov.: 27 AF XY: 0.000313 AC XY: 17 AN XY: 54250

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.000176

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000192

Gnomad4 OTH AF: 0.000661

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

Apr 01, 2024

CSNK2A1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs750062577; hg19: chr20-459409;