NM_000075.4:c.*776_*777dupAA
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2
The NM_000075.4(CDK4):c.*776_*777dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000859 in 151,408 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000061 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00081 ( 0 hom. )
Consequence
CDK4
NM_000075.4 3_prime_UTR
NM_000075.4 3_prime_UTR
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.674
Publications
0 publications found
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]
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]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
BS2
High AC in GnomAd4 at 9 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CDK4 | NM_000075.4 | c.*776_*777dupAA | 3_prime_UTR_variant | Exon 8 of 8 | ENST00000257904.11 | NP_000066.1 | ||
| TSPAN31 | NM_005981.5 | c.*469_*470dupTT | 3_prime_UTR_variant | Exon 6 of 6 | ENST00000257910.8 | NP_005972.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CDK4 | ENST00000257904.11 | c.*776_*777dupAA | 3_prime_UTR_variant | Exon 8 of 8 | 1 | NM_000075.4 | ENSP00000257904.5 | |||
| TSPAN31 | ENST00000257910.8 | c.*469_*470dupTT | 3_prime_UTR_variant | Exon 6 of 6 | 1 | NM_005981.5 | ENSP00000257910.3 |
Frequencies
GnomAD3 genomes 0.00000683 AC: 1AN: 146448Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
146448
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.000815 AC: 4AN: 4908Hom.: 0 Cov.: 0 AF XY: 0.00125 AC XY: 3AN XY: 2400 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
4
AN:
4908
Hom.:
Cov.:
0
AF XY:
AC XY:
3
AN XY:
2400
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
78
American (AMR)
AF:
AC:
0
AN:
396
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
240
East Asian (EAS)
AF:
AC:
0
AN:
632
South Asian (SAS)
AF:
AC:
1
AN:
234
European-Finnish (FIN)
AF:
AC:
0
AN:
16
Middle Eastern (MID)
AF:
AC:
0
AN:
26
European-Non Finnish (NFE)
AF:
AC:
3
AN:
3018
Other (OTH)
AF:
AC:
0
AN:
268
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000614 AC: 9AN: 146500Hom.: 1 Cov.: 31 AF XY: 0.0000280 AC XY: 2AN XY: 71354 show subpopulations
GnomAD4 genome
AF:
AC:
9
AN:
146500
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
71354
show subpopulations
African (AFR)
AF:
AC:
0
AN:
40122
American (AMR)
AF:
AC:
1
AN:
14676
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3390
East Asian (EAS)
AF:
AC:
0
AN:
5050
South Asian (SAS)
AF:
AC:
0
AN:
4612
European-Finnish (FIN)
AF:
AC:
0
AN:
9248
Middle Eastern (MID)
AF:
AC:
0
AN:
282
European-Non Finnish (NFE)
AF:
AC:
0
AN:
66234
Other (OTH)
AF:
AC:
8
AN:
1988
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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