rs762810555
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004064.5(CDKN1B):c.492C>A(p.Asn164Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,860 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N164S) has been classified as Likely benign.
Frequency
Consequence
NM_004064.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN1B | NM_004064.5 | c.492C>A | p.Asn164Lys | missense_variant | 2/3 | ENST00000228872.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN1B | ENST00000228872.9 | c.492C>A | p.Asn164Lys | missense_variant | 2/3 | 1 | NM_004064.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461860Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727230
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 10, 2022 | ClinVar contains an entry for this variant (Variation ID: 1467671). This variant has not been reported in the literature in individuals affected with CDKN1B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 164 of the CDKN1B protein (p.Asn164Lys). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 21, 2022 | The p.N164K variant (also known as c.492C>A), located in coding exon 2 of the CDKN1B gene, results from a C to A substitution at nucleotide position 492. The asparagine at codon 164 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. 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