5-112839053-TGAA-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000038.6(APC):​c.3468_3470delAGA​(p.Glu1157del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00083 in 1,614,062 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00051 ( 5 hom. )

Consequence

APC
NM_000038.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:25

Conservation

PhyloP100: 7.96
Variant links:
Genes affected
APC (HGNC:583): (APC regulator of WNT signaling pathway) This gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. It is also involved in other processes including cell migration and adhesion, transcriptional activation, and apoptosis. Defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Mutations in the APC gene have been found to occur in most colorectal cancers, where disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. [provided by RefSeq, Jun 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 5-112839053-TGAA-T is Benign according to our data. Variant chr5-112839053-TGAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 41527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839053-TGAA-T is described in Lovd as [Pathogenic]. Variant chr5-112839053-TGAA-T is described in Lovd as [Likely_benign]. Variant chr5-112839053-TGAA-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00393 (599/152262) while in subpopulation AFR AF= 0.0138 (574/41558). AF 95% confidence interval is 0.0129. There are 6 homozygotes in gnomad4. There are 284 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 599 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
APCNM_000038.6 linkc.3468_3470delAGA p.Glu1157del disruptive_inframe_deletion Exon 16 of 16 ENST00000257430.9 NP_000029.2 P25054-1Q4LE70

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
APCENST00000257430.9 linkc.3468_3470delAGA p.Glu1157del disruptive_inframe_deletion Exon 16 of 16 5 NM_000038.6 ENSP00000257430.4 P25054-1
ENSG00000258864ENST00000520401.1 linkn.228+10090_228+10092delAGA intron_variant Intron 3 of 7 3 ENSP00000454861.1 H3BNH8

Frequencies

GnomAD3 genomes
AF:
0.00396
AC:
602
AN:
152144
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0139
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00526
GnomAD3 exomes
AF:
0.00101
AC:
253
AN:
250976
Hom.:
1
AF XY:
0.000818
AC XY:
111
AN XY:
135644
show subpopulations
Gnomad AFR exome
AF:
0.0128
Gnomad AMR exome
AF:
0.000665
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000970
Gnomad OTH exome
AF:
0.00163
GnomAD4 exome
AF:
0.000506
AC:
740
AN:
1461800
Hom.:
5
AF XY:
0.000435
AC XY:
316
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.0150
Gnomad4 AMR exome
AF:
0.000716
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000130
Gnomad4 OTH exome
AF:
0.000878
GnomAD4 genome
AF:
0.00393
AC:
599
AN:
152262
Hom.:
6
Cov.:
32
AF XY:
0.00382
AC XY:
284
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.0138
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.0000679
Hom.:
0
Bravo
AF:
0.00444
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign/Likely benign
Submissions summary: Uncertain:1Benign:25
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:6
Jul 13, 2012
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: research

- -

Oct 21, 2022
Quest Diagnostics Nichols Institute San Juan Capistrano
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Mar 29, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 22703879, 21488257, 24599579, 27153395, 24345752, 24113346, 29367705) -

-
Clinical Genetics, Academic Medical Center
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Dec 05, 2016
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Variant summary: The APC c.3468_3470delAGA (p.Glu1157del) variant causes deletion of a Glutamic acid in a run of 4 repetitive Glutamic acids. This variant was found in 148/121852 control chromosomes (1 homozygote), predominantly observed in the African subpopulation at a frequency of 0.0130777 (133/10170). This frequency is about 183 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. The variant of interest has been reported in patients with familial adenomatous polyposis including co-occurrences with other potentially pathogenic variants (Grandval_2014), supporting for the benign outcome. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as likely benign/benign. Taken together, this variant is classified as Benign. -

Jun 19, 2023
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Sep 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

APC: PM4:Supporting, BS1 -

not specified Benign:6
Aug 31, 2020
Genetic Services Laboratory, University of Chicago
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

May 30, 2017
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Nov 23, 2016
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Mar 04, 2025
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Familial adenomatous polyposis 1 Benign:5
Aug 02, 2021
St. Jude Molecular Pathology, St. Jude Children's Research Hospital
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Mar 20, 2024
Myriad Genetics, Inc.
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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. -

Jul 24, 2014
Pathway Genomics
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Feb 04, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jul 02, 2018
Mendelics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:5
Dec 09, 2014
Ambry Genetics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: 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. -

Aug 11, 2020
Sema4, Sema4
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: curation

- -

Mar 21, 2016
Color Diagnostics, LLC DBA Color Health
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Oct 25, 2017
True Health Diagnostics
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

May 16, 2023
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Familial multiple polyposis syndrome Benign:1
Nov 30, 2015
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

APC-Associated Polyposis Disorders Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Classic or attenuated familial adenomatous polyposis Benign:1
Feb 05, 2024
All of Us Research Program, National Institutes of Health
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

actually g.112174759_112174761del, c.3468_3470del, p.E1157del was c.3460_3462del, p.1154_1154del -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs386833391; hg19: chr5-112174750; API