10-60788340-G-C

Variant names:

• chr10-60788340-G-C
• rs2456772
• NM_001786.5:c.489+110G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001786.5(CDK1):​c.489+110G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 718,564 control chromosomes in the GnomAD database, including 200,631 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 0.74 (41759 hom., cov: 32)
  • Exomes 𝑓: 0.75 (158872 hom.)
• Consequence: CDK1 NM_001786.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676
• Publications: 5 publications found

Genes affected

CDK1 (HGNC:1722): (cyclin dependent kinase 1) The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is a catalytic subunit of the highly conserved protein kinase complex known as M-phase promoting factor (MPF), which is essential for G2/M phase transitions of eukaryotic cell cycle. Mitotic cyclins stably associate with this protein and function as regulatory subunits. The kinase activity of this protein is controlled by cyclin accumulation and destruction through the cell cycle. The phosphorylation and dephosphorylation of this protein also play important regulatory roles in cell cycle control. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2023]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001786.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK1	NM_001786.5	MANE Select	c.489+110G>C		intron	N/A	NP_001777.1	P06493-1
	CDK1	NM_001320918.1		c.489+110G>C		intron	N/A	NP_001307847.1	P06493-1
	CDK1	NM_033379.5		c.318+2553G>C		intron	N/A	NP_203698.1	P06493-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK1	ENST00000395284.8	TSL:1 MANE Select	c.489+110G>C		intron	N/A	ENSP00000378699.3	P06493-1
	CDK1	ENST00000448257.6	TSL:1	c.493+106G>C		intron	N/A	ENSP00000397973.2	A0A024QZP7
	CDK1	ENST00000373809.2	TSL:1	c.318+2553G>C		intron	N/A	ENSP00000362915.2	P06493-2

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112260 AN: 151804 Hom.: 41732 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.745

GnomAD4 exome AF: 0.747 AC: 423143 AN: 566642 Hom.: 158872 AF XY: 0.748 AC XY: 214502 AN XY: 286814

African (AFR) AF: 0.692 AC: 9531 AN: 13780

American (AMR) AF: 0.782 AC: 10851 AN: 13868

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 9620 AN: 12656

East Asian (EAS) AF: 0.805 AC: 23694 AN: 29430

South Asian (SAS) AF: 0.799 AC: 20857 AN: 26092

European-Finnish (FIN) AF: 0.841 AC: 32811 AN: 38998

Middle Eastern (MID) AF: 0.770 AC: 2784 AN: 3614

European-Non Finnish (NFE) AF: 0.729 AC: 291969 AN: 400448

Other (OTH) AF: 0.758 AC: 21026 AN: 27756

GnomAD4 genome AF: 0.739 AC: 112344 AN: 151922 Hom.: 41759 Cov.: 32 AF XY: 0.746 AC XY: 55394 AN XY: 74254

African (AFR) AF: 0.692 AC: 28689 AN: 41472

American (AMR) AF: 0.761 AC: 11617 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2605 AN: 3470

East Asian (EAS) AF: 0.838 AC: 4329 AN: 5168

South Asian (SAS) AF: 0.796 AC: 3832 AN: 4816

European-Finnish (FIN) AF: 0.845 AC: 8960 AN: 10602

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 49907 AN: 67810

Other (OTH) AF: 0.742 AC: 1565 AN: 2110

Alfa AF: 0.732 Hom.: 5041

Bravo AF: 0.731

Asia WGS AF: 0.774 AC: 2693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.55
PhyloP100		-0.68
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: rs2456772; hg19: chr10-62548098; COSMIC: COSV57349214; COSMIC: COSV57349214;