rs1493107

Variant names:

• chr6-53005522-A-C
• rs1493107
• NM_014920.5:c.1745-219T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-53005522-A-C
• chr6-53005522-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014920.5(CILK1):​c.1745-219T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 151,976 control chromosomes in the GnomAD database, including 7,721 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7721 hom., cov: 32)
• Consequence: CILK1 NM_014920.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00900
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 6-53005522-A-C is Benign according to our data. Variant chr6-53005522-A-C is described in ClinVar as [Benign]. Clinvar id is 1276683.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CILK1	NM_014920.5	c.1745-219T>G		intron_variant	Intron 13 of 13	ENST00000676107.1	NP_055735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CILK1	ENST00000676107.1	c.1745-219T>G		intron_variant	Intron 13 of 13		NM_014920.5	ENSP00000501692.1
CILK1	ENST00000350082.10	c.1766-219T>G		intron_variant	Intron 13 of 13	1		ENSP00000263043.8
CILK1	ENST00000356971.3	c.1745-219T>G		intron_variant	Intron 14 of 14	2		ENSP00000349458.3

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46505 AN: 151858 Hom.: 7686 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.306 AC: 46574 AN: 151976 Hom.: 7721 Cov.: 32 AF XY: 0.301 AC XY: 22379 AN XY: 74284

African (AFR) AF: 0.422 AC: 17498 AN: 41420

American (AMR) AF: 0.257 AC: 3925 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1121 AN: 3468

East Asian (EAS) AF: 0.139 AC: 719 AN: 5162

South Asian (SAS) AF: 0.177 AC: 853 AN: 4820

European-Finnish (FIN) AF: 0.283 AC: 2991 AN: 10566

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18625 AN: 67938

Other (OTH) AF: 0.301 AC: 634 AN: 2106

Alfa AF: 0.280 Hom.: 10436

Bravo AF: 0.311

Asia WGS AF: 0.167 AC: 581 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.36
PhyloP100		-0.0090
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: rs1493107; hg19: chr6-52870320;