20-478765-CAAAAAAAA-CAAAAAA

Variant names:

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

Variant summary

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

The ENST00000400227.8(CSNK2A1):​c.1061-7_1061-6delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0298 in 173,238 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 27)
  • Exomes 𝑓: 0.087 (0 hom.)
• Consequence: CSNK2A1 ENST00000400227.8 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.725

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: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0862 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 30 AN: 113868 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000954

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: 0.00296

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000134

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0992 AC: 156 AN: 1572 Hom.: 0 AF XY: 0.106 AC XY: 102 AN XY: 958

Gnomad AFR exome AF: 0.0625

Gnomad AMR exome AF: 0.0892

Gnomad ASJ exome AF: 0.0500

Gnomad EAS exome AF: 0.102

Gnomad SAS exome AF: 0.102

Gnomad FIN exome AF: 0.250

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.0862

GnomAD4 exome AF: 0.0865 AC: 5140 AN: 59392 Hom.: 0 AF XY: 0.0863 AC XY: 3017 AN XY: 34954

Gnomad4 AFR exome AF: 0.0625

Gnomad4 AMR exome AF: 0.0868

Gnomad4 ASJ exome AF: 0.0837

Gnomad4 EAS exome AF: 0.0942

Gnomad4 SAS exome AF: 0.0843

Gnomad4 FIN exome AF: 0.0771

Gnomad4 NFE exome AF: 0.0889

Gnomad4 OTH exome AF: 0.0882

GnomAD4 genome AF: 0.000264 AC: 30 AN: 113846 Hom.: 0 Cov.: 27 AF XY: 0.000295 AC XY: 16 AN XY: 54210

Gnomad4 AFR AF: 0.0000952

Gnomad4 AMR AF: 0.000176

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00296

Gnomad4 NFE AF: 0.000134

Gnomad4 OTH AF: 0.00

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;