20-478765-CAAAAAAAA-CAAAA

Variant names:

• chr20-478765-CAAAA-C
• rs750062577
• NM_177559.3:c.*5192_*5195delTTTT

Variant summary

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

The ENST00000400227.8(CSNK2A1):​c.1061-9_1061-6delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 175,104 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 0.0000088 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0073 (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 = 0.00729 (446/61176) while in subpopulation EAS AF= 0.0183 (6/328). AF 95% confidence interval is 0.0094. There are 0 homozygotes in gnomad4_exome. There are 242 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 446 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK2A1	NM_177559.3	c.*5192_*5195delTTTT		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.*5192_*5195delTTTT		3_prime_UTR_variant	Exon 14 of 14	1	NM_177559.3	ENSP00000217244.3

Frequencies

GnomAD3 genomes AF: 0.00000878 AC: 1 AN: 113928 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

GnomAD3 exomes AF: 0.0140 AC: 22 AN: 1572 Hom.: 0 AF XY: 0.0115 AC XY: 11 AN XY: 958

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0249

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0204

Gnomad SAS exome AF: 0.00502

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.0109

Gnomad OTH exome AF: 0.0172

GnomAD4 exome AF: 0.00729 AC: 446 AN: 61176 Hom.: 0 AF XY: 0.00671 AC XY: 242 AN XY: 36092

Gnomad4 AFR exome AF: 0.00641

Gnomad4 AMR exome AF: 0.0142

Gnomad4 ASJ exome AF: 0.00367

Gnomad4 EAS exome AF: 0.0183

Gnomad4 SAS exome AF: 0.00662

Gnomad4 FIN exome AF: 0.00528

Gnomad4 NFE exome AF: 0.00757

Gnomad4 OTH exome AF: 0.00782

GnomAD4 genome AF: 0.00000878 AC: 1 AN: 113928 Hom.: 0 Cov.: 27 AF XY: 0.0000184 AC XY: 1 AN XY: 54218

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

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: 0.00

Bravo AF: 0.00000378

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;