rs3213083

Positions:

• chr10-60793872-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001786.5(CDK1):​c.796-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000694 in 1,467,240 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0039 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (2 hom.)
• Consequence: CDK1 NM_001786.5 splice_region, intron
• Scores: Splicing: ADA: 0.00009937
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BS2: High AC in GnomAd4 at 591 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK1	NM_001786.5	c.796-5C>T		splice_region_variant, intron_variant		ENST00000395284.8	NP_001777.1
CDK1	NM_001320918.1	c.796-5C>T		splice_region_variant, intron_variant			NP_001307847.1
CDK1	NM_033379.5	c.625-5C>T		splice_region_variant, intron_variant			NP_203698.1
CDK1	XM_005270303.4	c.796-5C>T		splice_region_variant, intron_variant			XP_005270360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK1	ENST00000395284.8	c.796-5C>T		splice_region_variant, intron_variant		1	NM_001786.5	ENSP00000378699.3
CDK1	ENST00000448257.6	c.796-5C>T		splice_region_variant, intron_variant		1		ENSP00000397973.2
CDK1	ENST00000373809.2	c.625-5C>T		splice_region_variant, intron_variant		1		ENSP00000362915.2
CDK1	ENST00000316629.8	c.625-5C>T		splice_region_variant, intron_variant		5		ENSP00000325970.4

Frequencies

GnomAD3 genomes AF: 0.00388 AC: 587 AN: 151406 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00184

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000886

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.000847 AC: 170 AN: 200636 Hom.: 2 AF XY: 0.000554 AC XY: 61 AN XY: 110164

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.000628

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000430

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000635

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000325 AC: 427 AN: 1315716 Hom.: 2 Cov.: 19 AF XY: 0.000270 AC XY: 178 AN XY: 660130

Gnomad4 AFR exome AF: 0.0120

Gnomad4 AMR exome AF: 0.000571

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000655

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000179

Gnomad4 OTH exome AF: 0.00101

GnomAD4 genome AF: 0.00390 AC: 591 AN: 151524 Hom.: 3 Cov.: 32 AF XY: 0.00369 AC XY: 273 AN XY: 74018

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.00184

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000886

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00163 Hom.: 1

Bravo AF: 0.00403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.9
DANN	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000099
dbscSNV1_RF	Benign	0.0040
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

Publications

LitVar

Other links and lift over

dbSNP: rs3213083; hg19: chr10-62553630;