chr12-12718106-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_004064.5(CDKN1B):c.267C>T(p.Tyr89=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000681 in 1,614,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
CDKN1B
NM_004064.5 synonymous
NM_004064.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.81
Genes affected
CDKN1B (HGNC:1785): (cyclin dependent kinase inhibitor 1B) This gene encodes a cyclin-dependent kinase inhibitor, which shares a limited similarity with CDK inhibitor CDKN1A/p21. The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. The degradation of this protein, which is triggered by its CDK dependent phosphorylation and subsequent ubiquitination by SCF complexes, is required for the cellular transition from quiescence to the proliferative state. Mutations in this gene are associated with multiple endocrine neoplasia type IV (MEN4). [provided by RefSeq, Apr 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 12-12718106-C-T is Benign according to our data. Variant chr12-12718106-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 412890.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=1.81 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN1B | NM_004064.5 | c.267C>T | p.Tyr89= | synonymous_variant | 1/3 | ENST00000228872.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN1B | ENST00000228872.9 | c.267C>T | p.Tyr89= | synonymous_variant | 1/3 | 1 | NM_004064.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152268Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250874Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135856
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461862Hom.: 0 Cov.: 51 AF XY: 0.00000963 AC XY: 7AN XY: 727236
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152386Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74524
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 15, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this variant does not alter splicing; Has not been previously published as pathogenic or benign to our knowledge - |
Multiple endocrine neoplasia type 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 03, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at