22-38312601-C-T

Variant names:

• chr22-38312601-C-T
• rs867198
• NM_152221.3:c.76+1481G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152221.3(CSNK1E):​c.76+1481G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 152,244 control chromosomes in the GnomAD database, including 573 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.076 (573 hom., cov: 33)
• Consequence: CSNK1E NM_152221.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.941
• Publications: 8 publications found

Genes affected

CSNK1E (HGNC:2453): (casein kinase 1 epsilon) The protein encoded by this gene is a serine/threonine protein kinase and a member of the casein kinase I protein family, whose members have been implicated in the control of cytoplasmic and nuclear processes, including DNA replication and repair. The encoded protein is found in the cytoplasm as a monomer and can phosphorylate a variety of proteins, including itself. This protein has been shown to phosphorylate period, a circadian rhythm protein. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2014]

TPTEP2-CSNK1E (HGNC:53829): (TPTEP2-CSNK1E readthrough) This locus represents naturally occurring readthrough transcription between the neighboring LOC400927 (transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 pseudogene) and CSNK1E (casein kinase I isoform epsilon) genes on chromosome 22. The readthrough transcript encodes the same protein as the downstream gene product (casein kinase I isoform epsilon). [provided by RefSeq, Feb 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152221.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1E	NM_152221.3	MANE Select	c.76+1481G>A		intron	N/A	NP_689407.1	P49674
	TPTEP2-CSNK1E	NM_001289912.2		c.76+1481G>A		intron	N/A	NP_001276841.1
	CSNK1E	NM_001894.5		c.76+1481G>A		intron	N/A	NP_001885.1	P49674

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1E	ENST00000396832.6	TSL:1 MANE Select	c.76+1481G>A		intron	N/A	ENSP00000380044.1	P49674
	CSNK1E	ENST00000359867.7	TSL:1	c.76+1481G>A		intron	N/A	ENSP00000352929.3	P49674
	TPTEP2-CSNK1E	ENST00000400206.7	TSL:2	c.76+1481G>A		intron	N/A	ENSP00000383067.2

Frequencies

GnomAD3 genomes AF: 0.0758 AC: 11534 AN: 152126 Hom.: 575 Cov.: 33

Gnomad AFR AF: 0.0703

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0309

Gnomad EAS AF: 0.0758

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0977

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0532

Gnomad OTH AF: 0.0608

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0758 AC: 11539 AN: 152244 Hom.: 573 Cov.: 33 AF XY: 0.0811 AC XY: 6040 AN XY: 74432

African (AFR) AF: 0.0701 AC: 2914 AN: 41558

American (AMR) AF: 0.174 AC: 2660 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0309 AC: 107 AN: 3468

East Asian (EAS) AF: 0.0759 AC: 393 AN: 5176

South Asian (SAS) AF: 0.136 AC: 659 AN: 4828

European-Finnish (FIN) AF: 0.0977 AC: 1036 AN: 10600

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0532 AC: 3616 AN: 68010

Other (OTH) AF: 0.0601 AC: 127 AN: 2112

Alfa AF: 0.0646 Hom.: 706

Bravo AF: 0.0821

Asia WGS AF: 0.111 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.28
DANN	Benign	0.77
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs867198; hg19: chr22-38708606;