rs3213056

Variant names:

• chr10-60788632-G-A
• rs3213056
• NM_001786.5:c.489+402G>A

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+402G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 152,098 control chromosomes in the GnomAD database, including 144 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 0.036 (144 hom., cov: 32)
• Consequence: CDK1 NM_001786.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK1	NM_001786.5	c.489+402G>A		intron_variant	Intron 5 of 7	ENST00000395284.8	NP_001777.1
CDK1	NM_001320918.1	c.489+402G>A		intron_variant	Intron 5 of 7		NP_001307847.1
CDK1	NM_033379.5	c.318+2845G>A		intron_variant	Intron 4 of 6		NP_203698.1
CDK1	XM_005270303.4	c.489+402G>A		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+402G>A		intron_variant	Intron 5 of 7	1	NM_001786.5	ENSP00000378699.3

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 5496 AN: 151980 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.00908

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0382

Gnomad ASJ AF: 0.0951

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0526

Gnomad OTH AF: 0.0570

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

GnomAD4 genome AF: 0.0361 AC: 5489 AN: 152098 Hom.: 144 Cov.: 32 AF XY: 0.0335 AC XY: 2493 AN XY: 74344

African (AFR) AF: 0.00905 AC: 376 AN: 41534

American (AMR) AF: 0.0381 AC: 582 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0951 AC: 330 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0112 AC: 54 AN: 4820

European-Finnish (FIN) AF: 0.0342 AC: 362 AN: 10590

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0525 AC: 3566 AN: 67906

Other (OTH) AF: 0.0565 AC: 119 AN: 2108

Alfa AF: 0.0467 Hom.: 98

Bravo AF: 0.0365

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.53
PhyloP100		-0.22
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: rs3213056; hg19: chr10-62548390;