rs2397136

Variant names:

• chr6-53001116-A-G
• rs2397136
• NM_014920.5:c.*4033T>C

Variant summary

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

The NM_014920.5(CILK1):​c.*4033T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,042 control chromosomes in the GnomAD database, including 3,321 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 0.20 (3321 hom., cov: 32)
• Consequence: CILK1 NM_014920.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343
• Publications: 4 publications found

Genes affected

CILK1 (HGNC:21219): (ciliogenesis associated kinase 1) Eukaryotic protein kinases are enzymes that belong to a very extensive family of proteins which share a conserved catalytic core common with both serine/threonine and tyrosine protein kinases. This gene encodes an intestinal serine/threonine kinase harboring a dual phosphorylation site found in mitogen-activating protein (MAP) kinases. The protein localizes to the intestinal crypt region and is thought to be important in intestinal epithelial cell proliferation and differentiation. Alternative splicing has been observed at this locus and two variants, encoding the same isoform, have been identified. [provided by RefSeq, Jul 2008]

CILK1 Gene-Disease associations (from GenCC):

• endocrine-cerebro-osteodysplasia syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• juvenile myoclonic epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014920.5. 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
	CILK1	NM_014920.5	MANE Select	c.*4033T>C		downstream_gene	N/A	NP_055735.1	Q9UPZ9-1
	CILK1	NM_001375397.1		c.*4033T>C		downstream_gene	N/A	NP_001362326.1	A0A7I2PIU1
	CILK1	NM_001375398.1		c.*4033T>C		downstream_gene	N/A	NP_001362327.1	Q9UPZ9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CILK1	ENST00000676107.1	MANE Select	c.*4033T>C		downstream_gene	N/A	ENSP00000501692.1	Q9UPZ9-1
	CILK1	ENST00000350082.10	TSL:1	c.*4033T>C		downstream_gene	N/A	ENSP00000263043.8	A0A7I2PIU1
	CILK1	ENST00000356971.3	TSL:2	c.*4033T>C		downstream_gene	N/A	ENSP00000349458.3	Q9UPZ9-1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29906 AN: 151924 Hom.: 3307 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.197 AC: 29940 AN: 152042 Hom.: 3321 Cov.: 32 AF XY: 0.191 AC XY: 14222 AN XY: 74340

African (AFR) AF: 0.295 AC: 12228 AN: 41436

American (AMR) AF: 0.176 AC: 2688 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3470

East Asian (EAS) AF: 0.0702 AC: 363 AN: 5172

South Asian (SAS) AF: 0.130 AC: 626 AN: 4820

European-Finnish (FIN) AF: 0.123 AC: 1296 AN: 10572

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11341 AN: 67968

Other (OTH) AF: 0.192 AC: 405 AN: 2114

Alfa AF: 0.181 Hom.: 4493

Bravo AF: 0.205

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.57
PhyloP100		-0.34

Splicing

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

Other links and lift over

dbSNP: rs2397136; hg19: chr6-52865914;