chr12-12718926-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004064.5(CDKN1B):c.577C>T(p.Leu193Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000607 in 1,614,064 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L193I) has been classified as Uncertain significance.
Frequency
Consequence
NM_004064.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN1B | NM_004064.5 | c.577C>T | p.Leu193Phe | missense_variant | 2/3 | ENST00000228872.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN1B | ENST00000228872.9 | c.577C>T | p.Leu193Phe | missense_variant | 2/3 | 1 | NM_004064.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00310 AC: 472AN: 152120Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000891 AC: 224AN: 251300Hom.: 0 AF XY: 0.000640 AC XY: 87AN XY: 135848
GnomAD4 exome AF: 0.000345 AC: 505AN: 1461826Hom.: 2 Cov.: 31 AF XY: 0.000319 AC XY: 232AN XY: 727206
GnomAD4 genome AF: 0.00311 AC: 474AN: 152238Hom.: 2 Cov.: 32 AF XY: 0.00301 AC XY: 224AN XY: 74442
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia type 4 Benign:4
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 24, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 04, 2022 | - - |
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | CDKN1B: BP4, BS1 - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 30, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 11, 2020 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Aug 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 22, 2019 | This alteration is classified as 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at