Variant 12-57748221-T-TA 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.*303_*304insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0764 in 314,530 control chromosomes in the GnomAD database, including 101 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.024 ( 101 hom., cov: 31)

Exomes 𝑓: 0.12 ( 0 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 = 0.0727 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.303_304insT		3_prime_UTR_variant	8/8	ENST00000257904.11
TSPAN31	NM_005981.5 linkuse as main transcript	c.*945dup		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.303_304insT		3_prime_UTR_variant	8/8	1	NM_000075.4	P1	P11802-1
TSPAN31	ENST00000257910.8 linkuse as main transcript	c.*945dup		3_prime_UTR_variant	6/6	1	NM_005981.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3266

AN:

137020

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0749

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00414

Gnomad SAS

AF:

0.00138

Gnomad FIN

AF:

0.00701

Gnomad MID

AF:

0.0106

Gnomad NFE

AF:

0.00221

Gnomad OTH

AF:

0.0191

GnomAD4 exome

AF:

0.117

AC:

20765

AN:

177474

Hom.:

Cov.:

AF XY:

0.116

AC XY:

10616

AN XY:

91596

show subpopulations

Gnomad4 AFR exome

AF:

0.135

Gnomad4 AMR exome

AF:

0.123

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.107

Gnomad4 SAS exome

AF:

0.106

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.0239

AC:

3277

AN:

137056

Hom.:

101

Cov.:

AF XY:

0.0237

AC XY:

1568

AN XY:

66190

show subpopulations

Gnomad4 AFR

AF:

0.0750

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00416

Gnomad4 SAS

AF:

0.00139

Gnomad4 FIN

AF:

0.00701

Gnomad4 NFE

AF:

0.00221

Gnomad4 OTH

AF:

0.0189

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