20-478765-CAAAAAAAA-CAAAAAAAAAAAAA

Variant names:

• chr20-478765-C-CAAAAA
• rs750062577
• NM_177559.3:c.*5191_*5195dupTTTTT

Variant summary

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

The ENST00000400227.8(CSNK2A1):​c.1061-10_1061-6dupTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000853 in 175,834 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 0.00011 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000048 (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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000105 (12/113932) while in subpopulation AFR AF= 0.000317 (10/31506). AF 95% confidence interval is 0.000172. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK2A1	NM_177559.3	c.*5191_*5195dupTTTTT		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.*5191_*5195dupTTTTT		3_prime_UTR_variant	Exon 14 of 14	1	NM_177559.3	ENSP00000217244.3

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 12 AN: 113954 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000318

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: 0.00

Gnomad OTH AF: 0.000663

GnomAD4 exome AF: 0.0000485 AC: 3 AN: 61902 Hom.: 0 Cov.: 0 AF XY: 0.0000548 AC XY: 2 AN XY: 36466

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000589

Gnomad4 OTH exome AF: 0.000370

GnomAD4 genome AF: 0.000105 AC: 12 AN: 113932 Hom.: 0 Cov.: 27 AF XY: 0.000129 AC XY: 7 AN XY: 54252

Gnomad4 AFR AF: 0.000317

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: 0.00

Gnomad4 OTH AF: 0.000661

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;