6-53036234-T-C

Variant names:

• chr6-53036234-T-C
• rs10484408
• NM_014920.5:c.156+1705A>G

Variant summary

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

The NM_014920.5(CILK1):​c.156+1705A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,166 control chromosomes in the GnomAD database, including 2,795 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 0.18 (2795 hom., cov: 32)
• Consequence: CILK1 NM_014920.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CILK1	NM_014920.5	MANE Select	c.156+1705A>G		intron	N/A	NP_055735.1
	CILK1	NM_001375397.1		c.156+1705A>G		intron	N/A	NP_001362326.1
	CILK1	NM_001375398.1		c.156+1705A>G		intron	N/A	NP_001362327.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CILK1	ENST00000676107.1	MANE Select	c.156+1705A>G		intron	N/A	ENSP00000501692.1
	CILK1	ENST00000350082.10	TSL:1	c.156+1705A>G		intron	N/A	ENSP00000263043.8
	CILK1	ENST00000356971.3	TSL:2	c.156+1705A>G		intron	N/A	ENSP00000349458.3

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27806 AN: 152048 Hom.: 2781 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0679

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.183 AC: 27844 AN: 152166 Hom.: 2795 Cov.: 32 AF XY: 0.178 AC XY: 13211 AN XY: 74418

African (AFR) AF: 0.257 AC: 10651 AN: 41496

American (AMR) AF: 0.167 AC: 2553 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 823 AN: 3470

East Asian (EAS) AF: 0.0681 AC: 353 AN: 5186

South Asian (SAS) AF: 0.112 AC: 540 AN: 4828

European-Finnish (FIN) AF: 0.122 AC: 1291 AN: 10586

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11143 AN: 67990

Other (OTH) AF: 0.181 AC: 382 AN: 2110

Alfa AF: 0.172 Hom.: 6577

Bravo AF: 0.190

Asia WGS AF: 0.0990 AC: 344 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.0
DANN	Benign	0.89
PhyloP100		-0.71
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: rs10484408; hg19: chr6-52901032;