Submissions for variant NM_000038.6(APC):c.423-4del

dbSNP: rs730881230

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel	RCV003148663	SCV003836622	benign	Familial adenomatous polyposis 1	2023-02-18	reviewed by expert panel	curation	The c.423-4del variant in APC is an intronic variant which results in the deletion of adenine at position -4 of intron 4. The highest allele frequency is 5.48% in gnomAD v3.1.2, which is higher than the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (HCCP VCEP) threshold for BA1 (0.1%). RNA assays showed no splicing mutation, indicating that this variant does not impact protein function (BS3_Supporting; PMID22447671). Finally, the results from more than or equal to 2 in silico splicing predictors support that this variant does not affect splicing (BP4). In summary, this variant meets the criteria to be classified as Benign for FAP based on the ACMG/AMP criteria applied, as specified by the HCCP VCEP: BA1, BS3_Supporting, BP4. (VCEP specifications version 1; date of approval: 12/12/2022).
GeneDx	RCV000159526	SCV000209483	benign	Hereditary cancer-predisposing syndrome	2014-03-27	criteria provided, single submitter	clinical testing	The variant is found in COLO-HEREDIC panel(s).
Ambry Genetics	RCV000159526	SCV000212933	benign	Hereditary cancer-predisposing syndrome	2020-07-07	criteria provided, single submitter	clinical testing	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.
Color Diagnostics, LLC DBA Color Health	RCV000159526	SCV000686966	likely benign	Hereditary cancer-predisposing syndrome	2017-07-13	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000159526	SCV000686968	benign	Hereditary cancer-predisposing syndrome	2016-03-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003148663	SCV001729424	benign	Familial adenomatous polyposis 1	2024-12-12	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001353891	SCV002011090	benign	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000159526	SCV002531960	benign	Hereditary cancer-predisposing syndrome	2020-01-30	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000202236	SCV002550560	likely benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002498791	SCV002808185	likely benign	Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach	2022-01-13	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003148663	SCV004931034	benign	Familial adenomatous polyposis 1	2024-02-23	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing.
Mayo Clinic Laboratories, Mayo Clinic	RCV000202236	SCV000256994	likely benign	not specified		no assertion criteria provided	research
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353891	SCV000591029	uncertain significance	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001353891	SCV001743864	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001353891	SCV001806851	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000202236	SCV001925185	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000202236	SCV002034223	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000202236	SCV002036494	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003975227	SCV004797387	benign	APC-related disorder	2023-11-07	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).