rs556682082
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001122630.2(CDKN1C):c.702G>A(p.Gly234=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000953 in 1,510,904 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00061 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000038 ( 0 hom. )
Consequence
CDKN1C
NM_001122630.2 synonymous
NM_001122630.2 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: -0.137
Genes affected
CDKN1C (HGNC:1786): (cyclin dependent kinase inhibitor 1C) This gene is imprinted, with preferential expression of the maternal allele. The encoded protein is a tight-binding, strong inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. Mutations in this gene are implicated in sporadic cancers and Beckwith-Wiedemann syndorome, suggesting that this gene is a tumor suppressor candidate. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 11-2884755-C-T is Benign according to our data. Variant chr11-2884755-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 412851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-2884755-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.137 with no splicing effect.
BS2
High AC in GnomAd4 at 93 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN1C | NM_001122630.2 | c.702G>A | p.Gly234= | synonymous_variant | 2/4 | ENST00000440480.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN1C | ENST00000440480.8 | c.702G>A | p.Gly234= | synonymous_variant | 2/4 | 1 | NM_001122630.2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000609 AC: 92AN: 151158Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000128 AC: 21AN: 164364Hom.: 0 AF XY: 0.0000637 AC XY: 6AN XY: 94252
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GnomAD4 exome AF: 0.0000375 AC: 51AN: 1359638Hom.: 0 Cov.: 31 AF XY: 0.0000355 AC XY: 24AN XY: 676464
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GnomAD4 genome AF: 0.000615 AC: 93AN: 151266Hom.: 0 Cov.: 33 AF XY: 0.000568 AC XY: 42AN XY: 73980
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Beckwith-Wiedemann syndrome Benign:2
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Feb 13, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Beckwith-Wiedemann syndrome;C1846009:IMAGe syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 19, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | CDKN1C: BP4, BP7, BS1 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
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