10-60792132-A-T

Position:

• chr10-60792132-A-T

Variant summary

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

The NM_001786.5(CDK1):​c.654-16A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 1,597,164 control chromosomes in the GnomAD database, including 477,806 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.78 (45901 hom., cov: 32)
  • Exomes 𝑓: 0.77 (431905 hom.)
• Consequence: CDK1 NM_001786.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but rather VUS (scored 4 / 10). Computational evidence support a benign effect (BayesDel_addAF=-0.866202).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK1	NM_001786.5	c.654-16A>T		intron_variant		ENST00000395284.8	NP_001777.1
CDK1	NM_001320918.1	c.654-16A>T		intron_variant			NP_001307847.1
CDK1	NM_033379.5	c.483-16A>T		intron_variant			NP_203698.1
CDK1	XM_005270303.4	c.654-16A>T		intron_variant			XP_005270360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK1	ENST00000395284.8	c.654-16A>T		intron_variant		1	NM_001786.5	ENSP00000378699.3
CDK1	ENST00000448257.6	c.654-16A>T		intron_variant		1		ENSP00000397973.2
CDK1	ENST00000373809.2	c.483-16A>T		intron_variant		1		ENSP00000362915.2
CDK1	ENST00000316629.8	c.483-16A>T		intron_variant		5		ENSP00000325970.4

Frequencies

GnomAD3 genomes AF: 0.777 AC: 117754 AN: 151514 Hom.: 45863 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.774

GnomAD3 exomes AF: 0.794 AC: 187930 AN: 236656 Hom.: 74771 AF XY: 0.794 AC XY: 101891 AN XY: 128324

Gnomad AFR exome AF: 0.757

Gnomad AMR exome AF: 0.797

Gnomad ASJ exome AF: 0.787

Gnomad EAS exome AF: 0.856

Gnomad SAS exome AF: 0.804

Gnomad FIN exome AF: 0.860

Gnomad NFE exome AF: 0.774

Gnomad OTH exome AF: 0.782

GnomAD4 exome AF: 0.772 AC: 1116496 AN: 1445534 Hom.: 431905 Cov.: 33 AF XY: 0.773 AC XY: 555387 AN XY: 718618

Gnomad4 AFR exome AF: 0.758

Gnomad4 AMR exome AF: 0.800

Gnomad4 ASJ exome AF: 0.790

Gnomad4 EAS exome AF: 0.813

Gnomad4 SAS exome AF: 0.804

Gnomad4 FIN exome AF: 0.860

Gnomad4 NFE exome AF: 0.763

Gnomad4 OTH exome AF: 0.785

GnomAD4 genome AF: 0.777 AC: 117848 AN: 151630 Hom.: 45901 Cov.: 32 AF XY: 0.782 AC XY: 57957 AN XY: 74074

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.839

Gnomad4 SAS AF: 0.802

Gnomad4 FIN AF: 0.867

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.771

Alfa AF: 0.770 Hom.: 8183

Bravo AF: 0.772

TwinsUK AF: 0.756 AC: 2805

ALSPAC AF: 0.753 AC: 2902

ESP6500AA AF: 0.761 AC: 3347

ESP6500EA AF: 0.759 AC: 6518

ExAC AF: 0.790 AC: 95780

Asia WGS AF: 0.786 AC: 2732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.26
FATHMM_MKL	Benign	0.099	N
GERP RS		1.1
BranchPoint Hunter		4.0

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: rs2456778; hg19: chr10-62551890; COSMIC: COSV57349951; COSMIC: COSV57349951;