rs1997644

Variant names:

• chr22-38319217-G-A
• rs1997644
• ENST00000400206.7:c.-12-5048C>T

Variant summary

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

The NM_001289912.2(TPTEP2-CSNK1E):​c.-12-5048C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,984 control chromosomes in the GnomAD database, including 16,013 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 0.44 (16013 hom., cov: 31)
• Consequence: TPTEP2-CSNK1E NM_001289912.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• Publications: 17 publications found

Genes affected

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]

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]

CSNK1E Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289912.2. 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
	TPTEP2-CSNK1E	NM_001289912.2		c.-12-5048C>T		intron	N/A	NP_001276841.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPTEP2-CSNK1E	ENST00000400206.7	TSL:2	c.-12-5048C>T		intron	N/A	ENSP00000383067.2
	CSNK1E	ENST00000922680.1		c.-13+776C>T		intron	N/A	ENSP00000592739.1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66698 AN: 151866 Hom.: 16001 Cov.: 31

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.439 AC: 66735 AN: 151984 Hom.: 16013 Cov.: 31 AF XY: 0.443 AC XY: 32911 AN XY: 74274

African (AFR) AF: 0.245 AC: 10175 AN: 41470

American (AMR) AF: 0.457 AC: 6969 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1489 AN: 3468

East Asian (EAS) AF: 0.362 AC: 1865 AN: 5152

South Asian (SAS) AF: 0.415 AC: 2002 AN: 4820

European-Finnish (FIN) AF: 0.637 AC: 6729 AN: 10566

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35887 AN: 67934

Other (OTH) AF: 0.419 AC: 883 AN: 2108

Alfa AF: 0.493 Hom.: 71113

Bravo AF: 0.418

Asia WGS AF: 0.364 AC: 1267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.8
DANN	Benign	0.67
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1997644; hg19: chr22-38715222;