chr20-484233-T-C

Position:

• chr20-484233-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_177559.3(CSNK2A1):​c.1061-157A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00584 in 571,046 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (15 hom., cov: 32)
  • Exomes 𝑓: 0.0062 (84 hom.)
• Consequence: CSNK2A1 NM_177559.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.170

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 20-484233-T-C is Benign according to our data. Variant chr20-484233-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1203223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSNK2A1	NM_177559.3	c.1061-157A>G		intron_variant		ENST00000217244.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSNK2A1	ENST00000217244.9	c.1061-157A>G		intron_variant		1	NM_177559.3	P1

Frequencies

GnomAD3 genomes AF: 0.00474 AC: 721 AN: 152202 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0856

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.0113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00625 AC: 2617 AN: 418726 Hom.: 84 AF XY: 0.00591 AC XY: 1270 AN XY: 215020

Gnomad4 AFR exome AF: 0.000213

Gnomad4 AMR exome AF: 0.00647

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0780

Gnomad4 SAS exome AF: 0.00216

Gnomad4 FIN exome AF: 0.0101

Gnomad4 NFE exome AF: 0.000671

Gnomad4 OTH exome AF: 0.00628

GnomAD4 genome AF: 0.00470 AC: 716 AN: 152320 Hom.: 15 Cov.: 32 AF XY: 0.00573 AC XY: 427 AN XY: 74474

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.00359

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0852

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.0113

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00180 Hom.: 0

Bravo AF: 0.00455

Asia WGS AF: 0.0350 AC: 120 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 24, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12625429; hg19: chr20-464877;