6-53016077-GAA-GA

Position:

• chr6-53016077-GAA-GA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_014920.5(CILK1):​c.831+5delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,613,750 control chromosomes in the GnomAD database, including 32 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (16 hom., cov: 33)
  • Exomes 𝑓: 0.00066 (16 hom.)
• Consequence: CILK1 NM_014920.5 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.286

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 6-53016077-GA-G is Benign according to our data. Variant chr6-53016077-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 199140.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00651 (991/152284) while in subpopulation AFR AF= 0.0229 (950/41558). AF 95% confidence interval is 0.0217. There are 16 homozygotes in gnomad4. There are 451 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 16 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CILK1	NM_014920.5	c.831+5delT		splice_region_variant, intron_variant		ENST00000676107.1	NP_055735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CILK1	ENST00000676107.1	c.831+5delT		splice_region_variant, intron_variant			NM_014920.5	ENSP00000501692.1
CILK1	ENST00000350082.10	c.831+5delT		splice_region_variant, intron_variant		1		ENSP00000263043.8
CILK1	ENST00000356971.3	c.831+5delT		splice_region_variant, intron_variant		2		ENSP00000349458.3

Frequencies

GnomAD3 genomes AF: 0.00649 AC: 987 AN: 152166 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.0228

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00173 AC: 436 AN: 251376 Hom.: 5 AF XY: 0.00136 AC XY: 185 AN XY: 135854

Gnomad AFR exome AF: 0.0240

Gnomad AMR exome AF: 0.000954

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000658 AC: 962 AN: 1461466 Hom.: 16 Cov.: 31 AF XY: 0.000564 AC XY: 410 AN XY: 727056

Gnomad4 AFR exome AF: 0.0242

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.000306

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00123

GnomAD4 genome AF: 0.00651 AC: 991 AN: 152284 Hom.: 16 Cov.: 33 AF XY: 0.00606 AC XY: 451 AN XY: 74444

Gnomad4 AFR AF: 0.0229

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00337 Hom.: 0

Bravo AF: 0.00727

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 03, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jul 17, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 23, 2023	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 17, 2015

- -

CILK1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 13, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs200780900; hg19: chr6-52880875;