22-38302851-G-A

Variant names:

• chr22-38302851-G-A
• rs186918102
• NM_152221.3:c.336+10C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_152221.3(CSNK1E):​c.336+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000475 in 1,613,808 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00030 (4 hom.)
• Consequence: CSNK1E NM_152221.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.438
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 22-38302851-G-A is Benign according to our data. Variant chr22-38302851-G-A is described in ClinVar as Benign. ClinVar VariationId is 724803.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 324 AD gene.

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.336+10C>T		intron	N/A	NP_689407.1	P49674
	TPTEP2-CSNK1E	NM_001289912.2		c.336+10C>T		intron	N/A	NP_001276841.1
	CSNK1E	NM_001894.5		c.336+10C>T		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.336+10C>T		intron	N/A	ENSP00000380044.1	P49674
	CSNK1E	ENST00000359867.7	TSL:1	c.336+10C>T		intron	N/A	ENSP00000352929.3	P49674
	TPTEP2-CSNK1E	ENST00000400206.7	TSL:2	c.336+10C>T		intron	N/A	ENSP00000383067.2

Frequencies

GnomAD3 genomes AF: 0.00213 AC: 324 AN: 152214 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00750

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000639 AC: 160 AN: 250570 AF XY: 0.000502

Gnomad AFR exome AF: 0.00733

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000796

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000302 AC: 442 AN: 1461474 Hom.: 4 Cov.: 30 AF XY: 0.000260 AC XY: 189 AN XY: 727006

African (AFR) AF: 0.00803 AC: 269 AN: 33480

American (AMR) AF: 0.000291 AC: 13 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000823 AC: 71 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5764

European-Non Finnish (NFE) AF: 0.0000540 AC: 60 AN: 1111848

Other (OTH) AF: 0.000398 AC: 24 AN: 60370

GnomAD4 genome AF: 0.00213 AC: 324 AN: 152334 Hom.: 2 Cov.: 33 AF XY: 0.00212 AC XY: 158 AN XY: 74478

African (AFR) AF: 0.00748 AC: 311 AN: 41570

American (AMR) AF: 0.000261 AC: 4 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68032

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00118 Hom.: 0

Bravo AF: 0.00231

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.3
DANN	Benign	0.77
PhyloP100		0.44
PromoterAI		-0.012	Neutral
Mutation Taster		=100/0	polymorphism

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: rs186918102; hg19: chr22-38698856; COSMIC: COSV104664222; COSMIC: COSV104664222;