12-57752598-C-T

Variant names:

• chr12-57752598-C-T
• rs238532
• ENST00000552862.1:c.-19-862G>A

Variant summary

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

The ENST00000552862.1(CDK4):​c.-19-862G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00445 in 152,390 control chromosomes in the GnomAD database, including 3 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 0.0044 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (0 hom.)
• Consequence: CDK4 ENST00000552862.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BS2: High AC in GnomAd4 at 677 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK4	ENST00000552862.1	c.-19-862G>A		intron_variant	Intron 1 of 2	3		ENSP00000446763.1
CDK4	ENST00000312990.10	c.-443G>A		upstream_gene_variant		1		ENSP00000316889.6
CDK4	ENST00000551706.1	n.-234G>A		upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.00444 AC: 676 AN: 152092 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000725

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00701

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00556 AC: 1 AN: 180 Hom.: 0 AF XY: 0.00758 AC XY: 1 AN XY: 132

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00725

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00445 AC: 677 AN: 152210 Hom.: 3 Cov.: 32 AF XY: 0.00451 AC XY: 336 AN XY: 74422

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00702

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00224 Hom.: 0

Bravo AF: 0.00467

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs238532; hg19: chr12-58146381;