6-53014897-C-T

Variant names:

• chr6-53014897-C-T
• rs316144
• NM_014920.5:c.832-915G>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.832-915G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 152,086 control chromosomes in the GnomAD database, including 28,777 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 0.58 (28777 hom., cov: 32)
• Consequence: CILK1 NM_014920.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 8 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 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.832-915G>A		intron	N/A	NP_055735.1	Q9UPZ9-1
	CILK1	NM_001375397.1		c.832-915G>A		intron	N/A	NP_001362326.1	A0A7I2PIU1
	CILK1	NM_001375398.1		c.832-915G>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.832-915G>A		intron	N/A	ENSP00000501692.1	Q9UPZ9-1
	CILK1	ENST00000350082.10	TSL:1	c.832-915G>A		intron	N/A	ENSP00000263043.8	A0A7I2PIU1
	CILK1	ENST00000356971.3	TSL:2	c.832-915G>A		intron	N/A	ENSP00000349458.3	Q9UPZ9-1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87855 AN: 151968 Hom.: 28709 Cov.: 32

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.579 AC: 87985 AN: 152086 Hom.: 28777 Cov.: 32 AF XY: 0.570 AC XY: 42385 AN XY: 74338

African (AFR) AF: 0.895 AC: 37155 AN: 41520

American (AMR) AF: 0.607 AC: 9277 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1750 AN: 3472

East Asian (EAS) AF: 0.360 AC: 1862 AN: 5170

South Asian (SAS) AF: 0.325 AC: 1563 AN: 4816

European-Finnish (FIN) AF: 0.408 AC: 4301 AN: 10544

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30507 AN: 67980

Other (OTH) AF: 0.549 AC: 1153 AN: 2100

Alfa AF: 0.495 Hom.: 65394

Bravo AF: 0.609

Asia WGS AF: 0.374 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.20
PhyloP100		-0.49
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: rs316144; hg19: chr6-52879695;