22-38299401-C-T

Variant names:

• chr22-38299401-C-T
• rs5750581
• NM_152221.3:c.737-467G>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.737-467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,298 control chromosomes in the GnomAD database, including 60,403 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 0.89 (60403 hom., cov: 34)
• Consequence: CSNK1E NM_152221.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK1E	NM_152221.3	c.737-467G>A		intron_variant	Intron 6 of 10	ENST00000396832.6	NP_689407.1
TPTEP2-CSNK1E	NM_001289912.2	c.737-467G>A		intron_variant	Intron 10 of 14		NP_001276841.1
CSNK1E	NM_001894.5	c.737-467G>A		intron_variant	Intron 6 of 10		NP_001885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1E	ENST00000396832.6	c.737-467G>A		intron_variant	Intron 6 of 10	1	NM_152221.3	ENSP00000380044.1
TPTEP2-CSNK1E	ENST00000400206.7	c.737-467G>A		intron_variant	Intron 10 of 14	2		ENSP00000383067.2

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135423 AN: 152180 Hom.: 60333 Cov.: 34

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.853

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

GnomAD4 genome AF: 0.890 AC: 135554 AN: 152298 Hom.: 60403 Cov.: 34 AF XY: 0.890 AC XY: 66278 AN XY: 74472

African (AFR) AF: 0.929 AC: 38628 AN: 41568

American (AMR) AF: 0.906 AC: 13866 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2867 AN: 3470

East Asian (EAS) AF: 0.900 AC: 4672 AN: 5192

South Asian (SAS) AF: 0.800 AC: 3859 AN: 4826

European-Finnish (FIN) AF: 0.902 AC: 9577 AN: 10614

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.871 AC: 59257 AN: 68008

Other (OTH) AF: 0.855 AC: 1810 AN: 2116

Alfa AF: 0.877 Hom.: 83927

Bravo AF: 0.898

Asia WGS AF: 0.863 AC: 2999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.69
DANN	Benign	0.35
PhyloP100		0.0040
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: rs5750581; hg19: chr22-38695406;