10-60794005-A-G

Variant names:

• chr10-60794005-A-G
• rs1871446
• NM_001786.5:c.*30A>G

Variant summary

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

The NM_001786.5(CDK1):​c.*30A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 1,041,966 control chromosomes in the GnomAD database, including 304,787 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 0.75 (43186 hom., cov: 32)
  • Exomes 𝑓: 0.77 (261601 hom.)
• Consequence: CDK1 NM_001786.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 20 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=-0.85).
• 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.*30A>G		3_prime_UTR	Exon 8 of 8	NP_001777.1	P06493-1
	CDK1	NM_001320918.1		c.*30A>G		3_prime_UTR	Exon 8 of 8	NP_001307847.1	P06493-1
	CDK1	NM_033379.5		c.*30A>G		3_prime_UTR	Exon 7 of 7	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.*30A>G		3_prime_UTR	Exon 8 of 8	ENSP00000378699.3	P06493-1
	CDK1	ENST00000448257.6	TSL:1	c.*30A>G		3_prime_UTR	Exon 8 of 8	ENSP00000397973.2	A0A024QZP7
	CDK1	ENST00000373809.2	TSL:1	c.*30A>G		3_prime_UTR	Exon 6 of 6	ENSP00000362915.2	P06493-2

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114169 AN: 151766 Hom.: 43158 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.766

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.760

GnomAD2 exomes AF: 0.779 AC: 137089 AN: 175962 AF XY: 0.780

Gnomad AFR exome AF: 0.692

Gnomad AMR exome AF: 0.782

Gnomad ASJ exome AF: 0.778

Gnomad EAS exome AF: 0.851

Gnomad FIN exome AF: 0.846

Gnomad NFE exome AF: 0.761

Gnomad OTH exome AF: 0.768

GnomAD4 exome AF: 0.765 AC: 681143 AN: 890082 Hom.: 261601 Cov.: 11 AF XY: 0.766 AC XY: 355273 AN XY: 464090

African (AFR) AF: 0.702 AC: 12244 AN: 17452

American (AMR) AF: 0.787 AC: 18716 AN: 23778

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 15908 AN: 20328

East Asian (EAS) AF: 0.803 AC: 25226 AN: 31420

South Asian (SAS) AF: 0.802 AC: 50700 AN: 63196

European-Finnish (FIN) AF: 0.845 AC: 44173 AN: 52254

Middle Eastern (MID) AF: 0.770 AC: 3370 AN: 4378

European-Non Finnish (NFE) AF: 0.753 AC: 479546 AN: 636826

Other (OTH) AF: 0.773 AC: 31260 AN: 40450

GnomAD4 genome AF: 0.752 AC: 114254 AN: 151884 Hom.: 43186 Cov.: 32 AF XY: 0.758 AC XY: 56280 AN XY: 74238

African (AFR) AF: 0.698 AC: 28933 AN: 41444

American (AMR) AF: 0.775 AC: 11826 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.773 AC: 2679 AN: 3466

East Asian (EAS) AF: 0.837 AC: 4338 AN: 5180

South Asian (SAS) AF: 0.800 AC: 3860 AN: 4824

European-Finnish (FIN) AF: 0.852 AC: 9016 AN: 10576

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51078 AN: 67826

Other (OTH) AF: 0.757 AC: 1598 AN: 2112

Alfa AF: 0.749 Hom.: 22792

Bravo AF: 0.745

Asia WGS AF: 0.776 AC: 2685 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.56
PhyloP100		-0.069
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1871446; hg19: chr10-62553763; COSMIC: COSV57349189; COSMIC: COSV57349189;