20-478765-CAAAAAAAA-CAAAAA

Variant names:

• chr20-478765-CAAA-C
• rs750062577
• NM_177559.3:c.*5193_*5195delTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000400227.8(CSNK2A1):​c.1061-8_1061-6delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00838 in 174,372 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 0.000026 (0 hom., cov: 27)
  • Exomes 𝑓: 0.024 (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.

• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0241 (1458/60452) while in subpopulation EAS AF= 0.0373 (12/322). AF 95% confidence interval is 0.0235. There are 0 homozygotes in gnomad4_exome. There are 837 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 1458 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK2A1	NM_177559.3	c.*5193_*5195delTTT		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.*5193_*5195delTTT		3_prime_UTR_variant	Exon 14 of 14	1	NM_177559.3	ENSP00000217244.3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 3 AN: 113920 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000880

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: 0.0000384

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0388 AC: 61 AN: 1572 Hom.: 0 AF XY: 0.0324 AC XY: 31 AN XY: 958

Gnomad AFR exome AF: 0.0625

Gnomad AMR exome AF: 0.0353

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0816

Gnomad SAS exome AF: 0.0351

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0435

Gnomad OTH exome AF: 0.0172

GnomAD4 exome AF: 0.0241 AC: 1458 AN: 60452 Hom.: 0 AF XY: 0.0235 AC XY: 837 AN XY: 35572

Gnomad4 AFR exome AF: 0.0290

Gnomad4 AMR exome AF: 0.0274

Gnomad4 ASJ exome AF: 0.0269

Gnomad4 EAS exome AF: 0.0373

Gnomad4 SAS exome AF: 0.0216

Gnomad4 FIN exome AF: 0.0257

Gnomad4 NFE exome AF: 0.0249

Gnomad4 OTH exome AF: 0.0237

GnomAD4 genome AF: 0.0000263 AC: 3 AN: 113920 Hom.: 0 Cov.: 27 AF XY: 0.0000553 AC XY: 3 AN XY: 54222

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000880

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000384

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;