6-53005376-G-C

Variant names:

• chr6-53005376-G-C
• rs2039214
• NM_014920.5:c.1745-73C>G

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.1745-73C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 1,529,926 control chromosomes in the GnomAD database, including 284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (157 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (127 hom.)
• Consequence: CILK1 NM_014920.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.224
• Publications: 0 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=-0.87).
• BP6: Variant 6-53005376-G-C is Benign according to our data. Variant chr6-53005376-G-C is described in ClinVar as [Benign]. Clinvar id is 1222700.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CILK1	NM_014920.5	c.1745-73C>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.1745-73C>G		intron_variant	Intron 13 of 13		NM_014920.5	ENSP00000501692.1
CILK1	ENST00000350082.10	c.1766-73C>G		intron_variant	Intron 13 of 13	1		ENSP00000263043.8
CILK1	ENST00000356971.3	c.1745-73C>G		intron_variant	Intron 14 of 14	2		ENSP00000349458.3

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3679 AN: 152092 Hom.: 157 Cov.: 32

Gnomad AFR AF: 0.0842

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00884

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.00258 AC: 3557 AN: 1377716 Hom.: 127 AF XY: 0.00224 AC XY: 1541 AN XY: 688398

African (AFR) AF: 0.0887 AC: 2822 AN: 31808

American (AMR) AF: 0.00588 AC: 248 AN: 42184

Ashkenazi Jewish (ASJ) AF: 0.0000393 AC: 1 AN: 25418

East Asian (EAS) AF: 0.00 AC: 0 AN: 39080

South Asian (SAS) AF: 0.000109 AC: 9 AN: 82780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52274

Middle Eastern (MID) AF: 0.00411 AC: 23 AN: 5602

European-Non Finnish (NFE) AF: 0.000134 AC: 139 AN: 1041008

Other (OTH) AF: 0.00547 AC: 315 AN: 57562

GnomAD4 genome AF: 0.0242 AC: 3684 AN: 152210 Hom.: 157 Cov.: 32 AF XY: 0.0229 AC XY: 1705 AN XY: 74410

African (AFR) AF: 0.0841 AC: 3492 AN: 41518

American (AMR) AF: 0.00883 AC: 135 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68006

Other (OTH) AF: 0.0157 AC: 33 AN: 2108

Alfa AF: 0.0204 Hom.: 11

Bravo AF: 0.0281

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 26, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.49
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism

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: rs2039214; hg19: chr6-52870174;