rs2448347

Variant names:

• chr10-60785384-G-A
• rs2448347
• NM_001786.5:c.195-280G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-60785384-G-A
• chr10-60785384-G-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.195-280G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,898 control chromosomes in the GnomAD database, including 15,922 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 0.45 (15922 hom., cov: 32)
• Consequence: CDK1 NM_001786.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 7 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 = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK1	NM_001786.5	c.195-280G>A		intron_variant	Intron 3 of 7	ENST00000395284.8	NP_001777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK1	ENST00000395284.8	c.195-280G>A		intron_variant	Intron 3 of 7	1	NM_001786.5	ENSP00000378699.3

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68857 AN: 151780 Hom.: 15906 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.454 AC: 68924 AN: 151898 Hom.: 15922 Cov.: 32 AF XY: 0.457 AC XY: 33948 AN XY: 74210

African (AFR) AF: 0.415 AC: 17197 AN: 41414

American (AMR) AF: 0.524 AC: 7997 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1408 AN: 3464

East Asian (EAS) AF: 0.700 AC: 3615 AN: 5162

South Asian (SAS) AF: 0.505 AC: 2432 AN: 4816

European-Finnish (FIN) AF: 0.501 AC: 5270 AN: 10518

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29518 AN: 67946

Other (OTH) AF: 0.452 AC: 955 AN: 2112

Alfa AF: 0.450 Hom.: 30434

Bravo AF: 0.461

Asia WGS AF: 0.561 AC: 1953 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.026
DANN	Benign	0.48
PhyloP100		-1.6
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: rs2448347; hg19: chr10-62545142;