rs587782888
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PM4_SupportingBP6
The NM_000038.6(APC):โc.4711_4713delโ(p.Asp1571del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000186 in 1,614,174 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. D1568D) has been classified as Likely benign.
Frequency
Consequence
NM_000038.6 inframe_deletion
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 |
---|---|---|---|---|---|---|---|
APC | NM_000038.6 | c.4711_4713del | p.Asp1571del | inframe_deletion | 16/16 | ENST00000257430.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APC | ENST00000257430.9 | c.4711_4713del | p.Asp1571del | inframe_deletion | 16/16 | 5 | NM_000038.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152230Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250660Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135506
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461826Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727228
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152348Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74498
ClinVar
Submissions by phenotype
Familial adenomatous polyposis 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 29, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | This variant, c.4711_4713del, results in the deletion of 1 amino acid(s) of the APC protein (p.Asp1571del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs587782888, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 143006). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 24, 2023 | The c.4711_4713delGAT variant (also known as p.D1571del) is located in coding exon 15 of the APC gene. This variant results from an in-frame GAT deletion at nucleotide positions 4711 to 4713. This results in the in-frame deletion of an aspartic acid at codon 1571. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jan 17, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 30, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Variant located in the 20-aa repeat B-catenin down-regulating domain and the SAMP repeats/axin binding domain (Azzopardi 2008); This variant is associated with the following publications: (PMID: 25980754) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at