rs2072052

Positions:

• chr12-57752936-A-C
• chr12-57752936-A-G
• chr12-57752936-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000552862.1(CDK4):​c.-19-1200T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,206 control chromosomes in the GnomAD database, including 6,776 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 0.26 (6776 hom., cov: 33)
• Consequence: CDK4 ENST00000552862.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587

Genes affected

CDK4 (HGNC:1773): (cyclin dependent kinase 4) The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK4	ENST00000552862.1	c.-19-1200T>G		intron_variant		3		ENSP00000446763

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40284 AN: 152088 Hom.: 6773 Cov.: 33

Gnomad AFR AF: 0.0785

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.265 AC: 40290 AN: 152206 Hom.: 6776 Cov.: 33 AF XY: 0.273 AC XY: 20303 AN XY: 74408

Gnomad4 AFR AF: 0.0783

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.653

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.236

Alfa AF: 0.273 Hom.: 1036

Bravo AF: 0.246

Asia WGS AF: 0.517 AC: 1794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.90

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2072052; hg19: chr12-58146719;