chr22-38296374-A-G

Position:

• chr22-38296374-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152221.3(CSNK1E):​c.886-1840T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 1,390,962 control chromosomes in the GnomAD database, including 3,345 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 0.074 (566 hom., cov: 33)
  • Exomes 𝑓: 0.062 (2779 hom.)
• Consequence: CSNK1E NM_152221.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSNK1E	NM_152221.3	c.886-1840T>C		intron_variant		ENST00000396832.6	NP_689407.1
TPTEP2-CSNK1E	NM_001289912.2	c.886-1840T>C		intron_variant			NP_001276841.1
CSNK1E	NM_001894.5	c.886-1840T>C		intron_variant			NP_001885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSNK1E	ENST00000396832.6	c.886-1840T>C		intron_variant		1	NM_152221.3	ENSP00000380044.1
TPTEP2-CSNK1E	ENST00000400206.7	c.886-1840T>C		intron_variant		2		ENSP00000383067.2

Frequencies

GnomAD3 genomes AF: 0.0745 AC: 11332 AN: 152152 Hom.: 568 Cov.: 33

Gnomad AFR AF: 0.0581

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.0771

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0538

Gnomad OTH AF: 0.0636

GnomAD4 exome AF: 0.0620 AC: 76836 AN: 1238692 Hom.: 2779 Cov.: 30 AF XY: 0.0628 AC XY: 37514 AN XY: 597514

Gnomad4 AFR exome AF: 0.0566

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.0335

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.0549

Gnomad4 OTH exome AF: 0.0648

GnomAD4 genome AF: 0.0745 AC: 11337 AN: 152270 Hom.: 566 Cov.: 33 AF XY: 0.0811 AC XY: 6037 AN XY: 74442

Gnomad4 AFR AF: 0.0580

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.0773

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0538

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0592 Hom.: 50

Bravo AF: 0.0790

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.056
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs3890379; hg19: chr22-38692380;