22-38294692-A-G

Variant names:

• chr22-38294692-A-G
• rs2075983
• NM_152221.3:c.886-158T>C

Variant summary

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

The NM_152221.3(CSNK1E):​c.886-158T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,014 control chromosomes in the GnomAD database, including 33,607 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 0.64 (33607 hom., cov: 31)
• Consequence: CSNK1E NM_152221.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1E	NM_152221.3	MANE Select	c.886-158T>C		intron	N/A	NP_689407.1
	TPTEP2-CSNK1E	NM_001289912.2		c.886-158T>C		intron	N/A	NP_001276841.1
	CSNK1E	NM_001894.5		c.886-158T>C		intron	N/A	NP_001885.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1E	ENST00000396832.6	TSL:1 MANE Select	c.886-158T>C		intron	N/A	ENSP00000380044.1
	CSNK1E	ENST00000359867.7	TSL:1	c.886-158T>C		intron	N/A	ENSP00000352929.3
	TPTEP2-CSNK1E	ENST00000400206.7	TSL:2	c.886-158T>C		intron	N/A	ENSP00000383067.2

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97559 AN: 151896 Hom.: 33594 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.642 AC: 97604 AN: 152014 Hom.: 33607 Cov.: 31 AF XY: 0.643 AC XY: 47762 AN XY: 74320

African (AFR) AF: 0.375 AC: 15529 AN: 41450

American (AMR) AF: 0.652 AC: 9956 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2641 AN: 3472

East Asian (EAS) AF: 0.809 AC: 4156 AN: 5136

South Asian (SAS) AF: 0.616 AC: 2955 AN: 4800

European-Finnish (FIN) AF: 0.785 AC: 8321 AN: 10598

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.761 AC: 51715 AN: 67964

Other (OTH) AF: 0.664 AC: 1406 AN: 2116

Alfa AF: 0.698 Hom.: 20885

Bravo AF: 0.627

Asia WGS AF: 0.682 AC: 2369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.13
DANN	Benign	0.57
PhyloP100		-0.36
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2075983; hg19: chr22-38690698;