rs529480958
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_000038.6(APC):c.4919G>A(p.Arg1640Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000681 in 1,614,126 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1640W) has been classified as Likely benign.
Frequency
Consequence
NM_000038.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APC | NM_000038.6 | c.4919G>A | p.Arg1640Gln | missense_variant | 16/16 | ENST00000257430.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APC | ENST00000257430.9 | c.4919G>A | p.Arg1640Gln | missense_variant | 16/16 | 5 | NM_000038.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000179 AC: 45AN: 251148Hom.: 0 AF XY: 0.000221 AC XY: 30AN XY: 135714
GnomAD4 exome AF: 0.0000677 AC: 99AN: 1461862Hom.: 1 Cov.: 66 AF XY: 0.0000908 AC XY: 66AN XY: 727230
GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152264Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74456
ClinVar
Submissions by phenotype
Familial adenomatous polyposis 1 Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Dec 04, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 23, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Feb 21, 2023 | This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Oct 28, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 25, 2018 | This variant is associated with the following publications: (PMID: 24599579, 24728327, 27978560, 25980754, 25186627, 29684080) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | APC: BS1 - |
Hereditary cancer-predisposing syndrome Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jun 15, 2016 | - - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | May 05, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2022 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not specified Benign:1Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 26, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at