rs12127944

chr1-205514467-C-Gchr1-205514467-C-T

Variant summary

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

The NM_212502.3(CDK18):c.-21-8680C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 152,198 control chromosomes in the GnomAD database, including 401 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 0.062 (401 hom., cov: 32)
• Consequence: CDK18 NM_212502.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

Genes affected

CDK18 (HGNC:8751): (cyclin dependent kinase 18) Predicted to enable ATP binding activity; cyclin-dependent protein serine/threonine kinase activity; and protein serine kinase activity. Predicted to be involved in protein phosphorylation and regulation of transcription involved in G1/S transition of mitotic cell cycle. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK18	NM_212502.3	c.-21-8680C>G		intron_variant		ENST00000429964.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK18	ENST00000429964.7	c.-21-8680C>G		intron_variant		1	NM_212502.3	P1

Frequencies

GnomAD3 genomes AF: 0.0621 AC: 9445 AN: 152080 Hom.: 400 Cov.: 32

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.0561

Gnomad FIN AF: 0.0830

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0904

Gnomad OTH AF: 0.0769

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

GnomAD4 genome AF: 0.0620 AC: 9442 AN: 152198 Hom.: 401 Cov.: 32 AF XY: 0.0614 AC XY: 4570 AN XY: 74408

Gnomad4 AFR AF: 0.0160

Gnomad4 AMR AF: 0.0567

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0133

Gnomad4 SAS AF: 0.0559

Gnomad4 FIN AF: 0.0830

Gnomad4 NFE AF: 0.0904

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0247 Hom.: 15

Bravo AF: 0.0592

Asia WGS AF: 0.0290 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	6.6
Dann	Benign	0.68

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: rs12127944; hg19: chr1-205483595;