22-38296374-A-G

Variant names:

• chr22-38296374-A-G
• rs3890379
• NM_152221.3:c.886-1840T>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.886-1840T>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
• Publications: 4 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 (AMR) allele frequency at 95% confidence interval = 0.17 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1E	NM_152221.3	MANE Select	c.886-1840T>C		intron	N/A	NP_689407.1	P49674
	TPTEP2-CSNK1E	NM_001289912.2		c.886-1840T>C		intron	N/A	NP_001276841.1
	CSNK1E	NM_001894.5		c.886-1840T>C		intron	N/A	NP_001885.1	P49674

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1E	ENST00000396832.6	TSL:1 MANE Select	c.886-1840T>C		intron	N/A	ENSP00000380044.1	P49674
	CSNK1E	ENST00000359867.7	TSL:1	c.886-1840T>C		intron	N/A	ENSP00000352929.3	P49674
	TPTEP2-CSNK1E	ENST00000400206.7	TSL:2	c.886-1840T>C		intron	N/A	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

African (AFR) AF: 0.0566 AC: 1513 AN: 26712

American (AMR) AF: 0.200 AC: 3195 AN: 15938

Ashkenazi Jewish (ASJ) AF: 0.0335 AC: 598 AN: 17876

East Asian (EAS) AF: 0.115 AC: 3625 AN: 31546

South Asian (SAS) AF: 0.110 AC: 6087 AN: 55092

European-Finnish (FIN) AF: 0.105 AC: 3064 AN: 29046

Middle Eastern (MID) AF: 0.0426 AC: 148 AN: 3474

European-Non Finnish (NFE) AF: 0.0549 AC: 55285 AN: 1007722

Other (OTH) AF: 0.0648 AC: 3321 AN: 51286

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

African (AFR) AF: 0.0580 AC: 2409 AN: 41560

American (AMR) AF: 0.176 AC: 2691 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3468

East Asian (EAS) AF: 0.0773 AC: 400 AN: 5176

South Asian (SAS) AF: 0.118 AC: 570 AN: 4834

European-Finnish (FIN) AF: 0.124 AC: 1312 AN: 10596

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0538 AC: 3660 AN: 68022

Other (OTH) AF: 0.0630 AC: 133 AN: 2112

Alfa AF: 0.0644 Hom.: 581

Bravo AF: 0.0790

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.056
DANN	Benign	0.68
PhyloP100		-2.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3890379;

hg19: chr22-38692380;