Variant 12-57748221-TA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000075.4(CDK4):c.*303del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 302,392 control chromosomes in the GnomAD database, including 424 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.051 ( 418 hom., cov: 31)

Exomes 𝑓: 0.24 ( 6 hom. )

Consequence

CDK4
NM_000075.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.557

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:

TSPAN31 (HGNC:10539): (tetraspanin 31) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is thought to be involved in growth-related cellular processes. This gene is associated with tumorigenesis and osteosarcoma. [provided by RefSeq, Jul 2008]

TSPAN31 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK4	NM_000075.4 linkuse as main transcript	c.*303del		3_prime_UTR_variant	8/8	ENST00000257904.11
TSPAN31	NM_005981.5 linkuse as main transcript	c.*945del		3_prime_UTR_variant	6/6	ENST00000257910.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK4	ENST00000257904.11 linkuse as main transcript	c.*303del		3_prime_UTR_variant	8/8	1	NM_000075.4	P1	P11802-1
TSPAN31	ENST00000257910.8 linkuse as main transcript	c.*945del		3_prime_UTR_variant	6/6	1	NM_005981.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0507

AC:

6929

AN:

136798

Hom.:

413

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0213

Gnomad ASJ

AF:

0.00249

Gnomad EAS

AF:

0.00581

Gnomad SAS

AF:

0.0711

Gnomad FIN

AF:

0.0171

Gnomad MID

AF:

0.0141

Gnomad NFE

AF:

0.00550

Gnomad OTH

AF:

0.0316

GnomAD4 exome

AF:

0.241

AC:

39908

AN:

165560

Hom.:

Cov.:

AF XY:

0.240

AC XY:

20617

AN XY:

85804

show subpopulations

Gnomad4 AFR exome

AF:

0.276

Gnomad4 AMR exome

AF:

0.267

Gnomad4 ASJ exome

AF:

0.228

Gnomad4 EAS exome

AF:

0.244

Gnomad4 SAS exome

AF:

0.257

Gnomad4 FIN exome

AF:

0.209

Gnomad4 NFE exome

AF:

0.236

Gnomad4 OTH exome

AF:

0.239

GnomAD4 genome

AF:

0.0509

AC:

6961

AN:

136832

Hom.:

418

Cov.:

AF XY:

0.0516

AC XY:

3408

AN XY:

66030

show subpopulations

Gnomad4 AFR

AF:

0.152

Gnomad4 AMR

AF:

0.0213

Gnomad4 ASJ

AF:

0.00249

Gnomad4 EAS

AF:

0.00583

Gnomad4 SAS

AF:

0.0720

Gnomad4 FIN

AF:

0.0171

Gnomad4 NFE

AF:

0.00550

Gnomad4 OTH

AF:

0.0390

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cutaneous Malignant Melanoma, Dominant

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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