rs1005473

Variant names:

• chr22-38298367-A-C
• rs1005473
• NM_152221.3:c.885+419T>G

Variant summary

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

The NM_152221.3(CSNK1E):​c.885+419T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 151,900 control chromosomes in the GnomAD database, including 548 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 0.072 (548 hom., cov: 32)
• Consequence: CSNK1E NM_152221.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18
• Publications: 13 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK1E	NM_152221.3	c.885+419T>G		intron_variant	Intron 7 of 10	ENST00000396832.6	NP_689407.1
TPTEP2-CSNK1E	NM_001289912.2	c.885+419T>G		intron_variant	Intron 11 of 14		NP_001276841.1
CSNK1E	NM_001894.5	c.885+419T>G		intron_variant	Intron 7 of 10		NP_001885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1E	ENST00000396832.6	c.885+419T>G		intron_variant	Intron 7 of 10	1	NM_152221.3	ENSP00000380044.1
TPTEP2-CSNK1E	ENST00000400206.7	c.885+419T>G		intron_variant	Intron 11 of 14	2		ENSP00000383067.2

Frequencies

GnomAD3 genomes AF: 0.0723 AC: 10969 AN: 151782 Hom.: 549 Cov.: 32

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.0738

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0525

Gnomad OTH AF: 0.0616

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

GnomAD4 genome AF: 0.0722 AC: 10972 AN: 151900 Hom.: 548 Cov.: 32 AF XY: 0.0790 AC XY: 5871 AN XY: 74284

African (AFR) AF: 0.0539 AC: 2233 AN: 41460

American (AMR) AF: 0.174 AC: 2655 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3468

East Asian (EAS) AF: 0.0740 AC: 380 AN: 5134

South Asian (SAS) AF: 0.116 AC: 556 AN: 4812

European-Finnish (FIN) AF: 0.123 AC: 1298 AN: 10518

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0525 AC: 3568 AN: 67926

Other (OTH) AF: 0.0610 AC: 128 AN: 2100

Alfa AF: 0.0605 Hom.: 56

Bravo AF: 0.0765

Asia WGS AF: 0.108 AC: 376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.6
DANN	Benign	0.72
PhyloP100		2.2
PromoterAI		-0.012	Neutral
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: rs1005473; hg19: chr22-38694373; COSMIC: COSV63290727; COSMIC: COSV63290727;