chr22-38307648-A-G

Variant names:

• chr22-38307648-A-G
• rs135757
• NM_152221.3:c.77-4400T>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.77-4400T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,210 control chromosomes in the GnomAD database, including 33,470 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 0.64 (33470 hom., cov: 33)
• Consequence: CSNK1E NM_152221.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• Publications: 17 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK1E	NM_152221.3	c.77-4400T>C		intron_variant	Intron 2 of 10	ENST00000396832.6	NP_689407.1
TPTEP2-CSNK1E	NM_001289912.2	c.77-4400T>C		intron_variant	Intron 6 of 14		NP_001276841.1
CSNK1E	NM_001894.5	c.77-4400T>C		intron_variant	Intron 2 of 10		NP_001885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1E	ENST00000396832.6	c.77-4400T>C		intron_variant	Intron 2 of 10	1	NM_152221.3	ENSP00000380044.1
TPTEP2-CSNK1E	ENST00000400206.7	c.77-4400T>C		intron_variant	Intron 6 of 14	2		ENSP00000383067.2

Frequencies

GnomAD3 genomes AF: 0.645 AC: 98038 AN: 152092 Hom.: 33455 Cov.: 33

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.644 AC: 98090 AN: 152210 Hom.: 33470 Cov.: 33 AF XY: 0.644 AC XY: 47903 AN XY: 74436

African (AFR) AF: 0.402 AC: 16698 AN: 41520

American (AMR) AF: 0.652 AC: 9968 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2595 AN: 3468

East Asian (EAS) AF: 0.799 AC: 4145 AN: 5186

South Asian (SAS) AF: 0.610 AC: 2946 AN: 4832

European-Finnish (FIN) AF: 0.755 AC: 7995 AN: 10594

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.756 AC: 51404 AN: 68010

Other (OTH) AF: 0.669 AC: 1414 AN: 2114

Alfa AF: 0.724 Hom.: 89261

Bravo AF: 0.632

Asia WGS AF: 0.670 AC: 2327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.1
DANN	Benign	0.86
PhyloP100		0.30
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: rs135757; hg19: chr22-38703653;