chr12-12717982-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004064.5(CDKN1B):āc.143A>Gā(p.His48Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H48Y) has been classified as Likely benign.
Frequency
Consequence
NM_004064.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN1B | NM_004064.5 | c.143A>G | p.His48Arg | missense_variant | 1/3 | ENST00000228872.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN1B | ENST00000228872.9 | c.143A>G | p.His48Arg | missense_variant | 1/3 | 1 | NM_004064.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461886Hom.: 0 Cov.: 50 AF XY: 0.00 AC XY: 0AN XY: 727242
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74344
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia type 4 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2023 | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 48 of the CDKN1B protein (p.His48Arg). This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 658567). This variant has not been reported in the literature in individuals affected with CDKN1B-related conditions. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 22, 2024 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 14, 2023 | The p.H48R variant (also known as c.143A>G), located in coding exon 1 of the CDKN1B gene, results from an A to G substitution at nucleotide position 143. The histidine at codon 48 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at