chr22-38300173-G-A

Variant names:

• chr22-38300173-G-A
• rs6001090
• NM_152221.3:c.566-108C>T

Variant summary

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

The NM_152221.3(CSNK1E):​c.566-108C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,029,526 control chromosomes in the GnomAD database, including 3,502 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 0.097 (2210 hom., cov: 33)
  • Exomes 𝑓: 0.014 (1292 hom.)
• Consequence: CSNK1E NM_152221.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658
• Publications: 2 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 = 0.319 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.566-108C>T		intron	N/A	NP_689407.1
	TPTEP2-CSNK1E	NM_001289912.2		c.566-108C>T		intron	N/A	NP_001276841.1
	CSNK1E	NM_001894.5		c.566-108C>T		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.566-108C>T		intron	N/A	ENSP00000380044.1
	CSNK1E	ENST00000359867.7	TSL:1	c.566-108C>T		intron	N/A	ENSP00000352929.3
	TPTEP2-CSNK1E	ENST00000400206.7	TSL:2	c.566-108C>T		intron	N/A	ENSP00000383067.2

Frequencies

GnomAD3 genomes AF: 0.0963 AC: 14641 AN: 152108 Hom.: 2201 Cov.: 33

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0386

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.0342

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.00332

Gnomad OTH AF: 0.0660

GnomAD4 exome AF: 0.0143 AC: 12505 AN: 877300 Hom.: 1292 AF XY: 0.0142 AC XY: 6284 AN XY: 442072

African (AFR) AF: 0.330 AC: 6713 AN: 20340

American (AMR) AF: 0.0261 AC: 613 AN: 23476

Ashkenazi Jewish (ASJ) AF: 0.00224 AC: 39 AN: 17394

East Asian (EAS) AF: 0.00847 AC: 284 AN: 33520

South Asian (SAS) AF: 0.0335 AC: 1942 AN: 58006

European-Finnish (FIN) AF: 0.0000287 AC: 1 AN: 34824

Middle Eastern (MID) AF: 0.0504 AC: 201 AN: 3986

European-Non Finnish (NFE) AF: 0.00234 AC: 1513 AN: 645604

Other (OTH) AF: 0.0299 AC: 1199 AN: 40150

GnomAD4 genome AF: 0.0965 AC: 14692 AN: 152226 Hom.: 2210 Cov.: 33 AF XY: 0.0946 AC XY: 7039 AN XY: 74422

African (AFR) AF: 0.324 AC: 13448 AN: 41526

American (AMR) AF: 0.0385 AC: 589 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3464

East Asian (EAS) AF: 0.0205 AC: 106 AN: 5182

South Asian (SAS) AF: 0.0334 AC: 161 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.00332 AC: 226 AN: 68014

Other (OTH) AF: 0.0658 AC: 139 AN: 2114

Alfa AF: 0.0400 Hom.: 933

Bravo AF: 0.108

Asia WGS AF: 0.0570 AC: 197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.31
DANN	Benign	0.53
PhyloP100		-0.66
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: rs6001090; hg19: chr22-38696178; COSMIC: COSV63290606; COSMIC: COSV63290606;