12-12717807-CGAGA-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_004064.5(CDKN1B):c.-29_-26delAGAG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000562 in 1,609,190 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004064.5 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000388 AC: 59AN: 152108Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000376 AC: 92AN: 244842Hom.: 0 AF XY: 0.000463 AC XY: 62AN XY: 133778
GnomAD4 exome AF: 0.000581 AC: 846AN: 1456964Hom.: 1 AF XY: 0.000584 AC XY: 423AN XY: 724762
GnomAD4 genome AF: 0.000388 AC: 59AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.000390 AC XY: 29AN XY: 74424
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia type 4 Pathogenic:1Benign:2
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not specified Uncertain:2
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not provided Uncertain:1Benign:1
Published functional studies demonstrate a damaging effect: decreased transcriptional activity, reduced p27 mRNA, and increased cytoplasmic localization (PMID: 22129891, 25645465, 27038812); Identified in patients with clinical features of Multiple Endocrine Neoplasia syndrome type 4 (MEN4) in published literature, but inherited from an unaffected parent in at least one family (PMID: 22129891, 25645465, 27038812, 32232325); Deleted nucleotides are not conserved across species; Also known as c.-32_-29del; This variant is associated with the following publications: (PMID: 27038812, 28824003, 25645465, 26054904, 27657986, 24819502, 30555957, 32232325, 34426522, 30065701, 35355569, 30990521, 36520683, 22129891) -
CDKN1B: PS3:Moderate, BP4, BS1 -
Primary hyperparathyroidism Pathogenic:1
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CDKN1B-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Multiple endocrine neoplasia Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at