10-60788916-T-C

Variant names:

• chr10-60788916-T-C
• rs1871445
• NM_001786.5:c.489+686T>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+686T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,940 control chromosomes in the GnomAD database, including 7,822 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 0.31 (7822 hom., cov: 32)
• Consequence: CDK1 NM_001786.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK1	NM_001786.5	c.489+686T>C		intron_variant	Intron 5 of 7	ENST00000395284.8	NP_001777.1
CDK1	NM_001320918.1	c.489+686T>C		intron_variant	Intron 5 of 7		NP_001307847.1
CDK1	NM_033379.5	c.319-2974T>C		intron_variant	Intron 4 of 6		NP_203698.1
CDK1	XM_005270303.4	c.489+686T>C		intron_variant	Intron 5 of 7		XP_005270360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK1	ENST00000395284.8	c.489+686T>C		intron_variant	Intron 5 of 7	1	NM_001786.5	ENSP00000378699.3

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47352 AN: 151824 Hom.: 7827 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.312 AC: 47376 AN: 151940 Hom.: 7822 Cov.: 32 AF XY: 0.313 AC XY: 23265 AN XY: 74224

African (AFR) AF: 0.260 AC: 10770 AN: 41464

American (AMR) AF: 0.371 AC: 5667 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 774 AN: 3468

East Asian (EAS) AF: 0.614 AC: 3165 AN: 5156

South Asian (SAS) AF: 0.334 AC: 1608 AN: 4814

European-Finnish (FIN) AF: 0.327 AC: 3450 AN: 10560

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20993 AN: 67878

Other (OTH) AF: 0.316 AC: 667 AN: 2110

Alfa AF: 0.309 Hom.: 9323

Bravo AF: 0.318

Asia WGS AF: 0.443 AC: 1543 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.70
PhyloP100		-0.18
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: rs1871445; hg19: chr10-62548674; COSMIC: COSV57349694; COSMIC: COSV57349694;