NM_014920.5:c.*4033T>C

Variant names:

• chr6-53001116-A-G
• rs2397136
• NM_014920.5:c.*4033T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014920.5(CILK1):​c.*4033T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,042 control chromosomes in the GnomAD database, including 3,321 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 0.20 (3321 hom., cov: 32)
• Consequence: CILK1 NM_014920.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CILK1	NM_014920.5	c.*4033T>C		downstream_gene_variant		ENST00000676107.1	NP_055735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CILK1	ENST00000676107.1	c.*4033T>C		downstream_gene_variant			NM_014920.5	ENSP00000501692.1
CILK1	ENST00000350082.10	c.*4033T>C		downstream_gene_variant		1		ENSP00000263043.8
CILK1	ENST00000356971.3	c.*4033T>C		downstream_gene_variant		2		ENSP00000349458.3

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29906 AN: 151924 Hom.: 3307 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.197 AC: 29940 AN: 152042 Hom.: 3321 Cov.: 32 AF XY: 0.191 AC XY: 14222 AN XY: 74340

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.0702

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.192

Alfa AF: 0.177 Hom.: 3337

Bravo AF: 0.205

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2397136; hg19: chr6-52865914;