Variant 12-57750882-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000075.4(CDK4):c.522+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,611,988 control chromosomes in the GnomAD database, including 95,898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6783 hom., cov: 32)

Exomes 𝑓: 0.34 ( 89115 hom. )

Consequence

CDK4
NM_000075.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.571

Variant links:

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]

CDK4 links:

CDK4 (HGNC:):

CDK4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 12-57750882-C-T is Benign according to our data. Variant chr12-57750882-C-T is described in ClinVar as [Benign]. Clinvar id is 1292556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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
CDK4	NM_000075.4 linkuse as main transcript	c.522+41G>A		intron_variant		ENST00000257904.11	NP_000066.1	P11802-1A0A024RBB6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK4	ENST00000257904.11 linkuse as main transcript	c.522+41G>A		intron_variant		1	NM_000075.4	ENSP00000257904.5		P11802-1

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40423

AN:

152044

Hom.:

6780

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0823

Gnomad AMI

AF:

0.382

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.652

Gnomad SAS

AF:

0.494

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.238

GnomAD3 exomes

AF:

0.355

AC:

89210

AN:

251364

Hom.:

17912

AF XY:

0.364

AC XY:

49429

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.0762

Gnomad AMR exome

AF:

0.345

Gnomad ASJ exome

AF:

0.278

Gnomad EAS exome

AF:

0.637

Gnomad SAS exome

AF:

0.497

Gnomad FIN exome

AF:

0.365

Gnomad NFE exome

AF:

0.321

Gnomad OTH exome

AF:

0.308

GnomAD4 exome

AF:

0.337

AC:

492646

AN:

1459826

Hom.:

89115

Cov.:

AF XY:

0.342

AC XY:

248628

AN XY:

726354

show subpopulations

Gnomad4 AFR exome

AF:

0.0710

Gnomad4 AMR exome

AF:

0.334

Gnomad4 ASJ exome

AF:

0.289

Gnomad4 EAS exome

AF:

0.702

Gnomad4 SAS exome

AF:

0.488

Gnomad4 FIN exome

AF:

0.357

Gnomad4 NFE exome

AF:

0.323

Gnomad4 OTH exome

AF:

0.322

GnomAD4 genome

AF:

0.266

AC:

40429

AN:

152162

Hom.:

6783

Cov.:

AF XY:

0.274

AC XY:

20381

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0821

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.289

Gnomad4 EAS

AF:

0.652

Gnomad4 SAS

AF:

0.494

Gnomad4 FIN

AF:

0.378

Gnomad4 NFE

AF:

0.316

Gnomad4 OTH

AF:

0.236

Alfa

AF:

0.304

Hom.:

11426

Bravo

AF:

0.247

Asia WGS

AF:

0.516

AC:

1792

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.74

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over