20-478765-CAAAAAAAA-CAAAAAAAAAA

Variant names:

• chr20-478765-C-CAA
• rs750062577
• NM_177559.3:c.*5194_*5195dupTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000400227.8(CSNK2A1):​c.1061-7_1061-6dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0176 in 175,552 control chromosomes in the GnomAD database, including 77 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.022 (77 hom., cov: 27)
  • Exomes 𝑓: 0.0090 (0 hom.)
• Consequence: CSNK2A1 ENST00000400227.8 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK2A1	NM_177559.3	c.*5194_*5195dupTT		3_prime_UTR_variant	Exon 14 of 14	ENST00000217244.9	NP_808227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK2A1	ENST00000217244	c.*5194_*5195dupTT		3_prime_UTR_variant	Exon 14 of 14	1	NM_177559.3	ENSP00000217244.3

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 2544 AN: 113914 Hom.: 77 Cov.: 27

Gnomad AFR AF: 0.0715

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.0171

Gnomad EAS AF: 0.000733

Gnomad SAS AF: 0.000284

Gnomad FIN AF: 0.000818

Gnomad MID AF: 0.0152

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.0166

GnomAD3 exomes AF: 0.00636 AC: 10 AN: 1572 Hom.: 0 AF XY: 0.00418 AC XY: 4 AN XY: 958

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00334

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00362

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00897 AC: 553 AN: 61658 Hom.: 0 Cov.: 0 AF XY: 0.00917 AC XY: 333 AN XY: 36310

Gnomad4 AFR exome AF: 0.0353

Gnomad4 AMR exome AF: 0.0156

Gnomad4 ASJ exome AF: 0.0156

Gnomad4 EAS exome AF: 0.00305

Gnomad4 SAS exome AF: 0.00919

Gnomad4 FIN exome AF: 0.00548

Gnomad4 NFE exome AF: 0.00863

Gnomad4 OTH exome AF: 0.00741

GnomAD4 genome AF: 0.0223 AC: 2545 AN: 113894 Hom.: 77 Cov.: 27 AF XY: 0.0215 AC XY: 1166 AN XY: 54232

Gnomad4 AFR AF: 0.0714

Gnomad4 AMR AF: 0.0130

Gnomad4 ASJ AF: 0.0171

Gnomad4 EAS AF: 0.000736

Gnomad4 SAS AF: 0.000286

Gnomad4 FIN AF: 0.000818

Gnomad4 NFE AF: 0.00121

Gnomad4 OTH AF: 0.0165

ClinVar

Not reported in ClinVar

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;