rs876658313
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000465.4(BARD1):c.439T>C(p.Phe147Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,276 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. F147I) has been classified as Uncertain significance.
Frequency
Consequence
NM_000465.4 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 |
---|---|---|---|---|---|---|---|
BARD1 | NM_000465.4 | c.439T>C | p.Phe147Leu | missense_variant | 4/11 | ENST00000260947.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BARD1 | ENST00000260947.9 | c.439T>C | p.Phe147Leu | missense_variant | 4/11 | 1 | NM_000465.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461276Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 726900
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Familial cancer of breast Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2017 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with BARD1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 147 of the BARD1 protein (p.Phe147Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 17, 2023 | The p.F147L variant (also known as c.439T>C), located in coding exon 4 of the BARD1 gene, results from a T to C substitution at nucleotide position 439. The phenylalanine at codon 147 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. 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