rs1871447

Variant names:

• chr10-60793572-G-A
• rs1871447
• NM_001786.5:c.796-305G>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.796-305G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,772 control chromosomes in the GnomAD database, including 7,646 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 (7646 hom., cov: 32)
• Consequence: CDK1 NM_001786.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK1	NM_001786.5	c.796-305G>A		intron_variant	Intron 7 of 7	ENST00000395284.8	NP_001777.1
CDK1	NM_001320918.1	c.796-305G>A		intron_variant	Intron 7 of 7		NP_001307847.1
CDK1	NM_033379.5	c.625-305G>A		intron_variant	Intron 6 of 6		NP_203698.1
CDK1	XM_005270303.4	c.796-305G>A		intron_variant	Intron 7 of 7		XP_005270360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK1	ENST00000395284.8	c.796-305G>A		intron_variant	Intron 7 of 7	1	NM_001786.5	ENSP00000378699.3
CDK1	ENST00000448257.6	c.796-305G>A		intron_variant	Intron 7 of 7	1		ENSP00000397973.2
CDK1	ENST00000373809.2	c.625-305G>A		intron_variant	Intron 5 of 5	1		ENSP00000362915.2
CDK1	ENST00000316629.8	c.625-305G>A		intron_variant	Intron 6 of 6	5		ENSP00000325970.4

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46702 AN: 151654 Hom.: 7649 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.308 AC: 46725 AN: 151772 Hom.: 7646 Cov.: 32 AF XY: 0.310 AC XY: 22957 AN XY: 74168

African (AFR) AF: 0.247 AC: 10207 AN: 41388

American (AMR) AF: 0.369 AC: 5627 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 773 AN: 3466

East Asian (EAS) AF: 0.615 AC: 3179 AN: 5166

South Asian (SAS) AF: 0.334 AC: 1610 AN: 4824

European-Finnish (FIN) AF: 0.327 AC: 3447 AN: 10548

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20947 AN: 67822

Other (OTH) AF: 0.310 AC: 654 AN: 2108

Alfa AF: 0.304 Hom.: 1223

Bravo AF: 0.314

Asia WGS AF: 0.444 AC: 1545 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.9
DANN	Benign	0.70
PhyloP100		0.19
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: rs1871447; hg19: chr10-62553330;