6-53031573-C-T

Variant names:

• chr6-53031573-C-T
• rs222455
• NM_014920.5:c.279-429G>A

Variant summary

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

The NM_014920.5(CILK1):​c.279-429G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,048 control chromosomes in the GnomAD database, including 37,863 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 0.70 (37863 hom., cov: 32)
• Consequence: CILK1 NM_014920.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.533
• Publications: 1 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.844 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.279-429G>A		intron	N/A	NP_055735.1	Q9UPZ9-1
	CILK1	NM_001375397.1		c.279-429G>A		intron	N/A	NP_001362326.1	A0A7I2PIU1
	CILK1	NM_001375398.1		c.279-429G>A		intron	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.279-429G>A		intron	N/A	ENSP00000501692.1	Q9UPZ9-1
	CILK1	ENST00000350082.10	TSL:1	c.279-429G>A		intron	N/A	ENSP00000263043.8	A0A7I2PIU1
	CILK1	ENST00000356971.3	TSL:2	c.279-429G>A		intron	N/A	ENSP00000349458.3	Q9UPZ9-1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106433 AN: 151930 Hom.: 37838 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.903

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.700 AC: 106484 AN: 152048 Hom.: 37863 Cov.: 32 AF XY: 0.706 AC XY: 52462 AN XY: 74326

African (AFR) AF: 0.586 AC: 24297 AN: 41466

American (AMR) AF: 0.754 AC: 11523 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2383 AN: 3472

East Asian (EAS) AF: 0.865 AC: 4467 AN: 5164

South Asian (SAS) AF: 0.850 AC: 4098 AN: 4824

European-Finnish (FIN) AF: 0.718 AC: 7581 AN: 10552

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.730 AC: 49616 AN: 67966

Other (OTH) AF: 0.708 AC: 1496 AN: 2112

Alfa AF: 0.728 Hom.: 22124

Bravo AF: 0.696

Asia WGS AF: 0.845 AC: 2941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.2
DANN	Benign	0.85
PhyloP100		0.53
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: rs222455; hg19: chr6-52896371;