5-112842788-C-T

Variant names:

• chr5-112842788-C-T
• rs565688379
• NM_000038.6:c.7194C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_000038.6(APC):​c.7194C>T​(p.Ser2398Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 32)
• Consequence: APC NM_000038.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.925
• Publications: 1 publications found

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]

APC Gene-Disease associations (from GenCC):

• classic or attenuated familial adenomatous polyposis

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• desmoid tumor

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp
• familial adenomatous polyposis 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
• gastric adenocarcinoma and proximal polyposis of the stomach

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• sarcoma

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• APC-related attenuated familial adenomatous polyposis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Turcot syndrome with polyposis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Cenani-Lenz syndactyly syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000258864 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-112842788-C-T is Benign according to our data. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112842788-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 215570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.925 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APC	NM_000038.6	c.7194C>T	p.Ser2398Ser	synonymous_variant	Exon 16 of 16	ENST00000257430.9	NP_000029.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000257430.9	c.7194C>T	p.Ser2398Ser	synonymous_variant	Exon 16 of 16	5	NM_000038.6	ENSP00000257430.4
ENSG00000258864	ENST00000520401.1	n.228+13816C>T		intron_variant	Intron 3 of 7	3		ENSP00000454861.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152100 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250172 AF XY: 0.00

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74428

African (AFR) AF: 0.0000723 AC: 3 AN: 41518

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 10, 2017

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Familial adenomatous polyposis 1 Benign:2

Apr 09, 2024

Myriad Genetics, Inc.

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -

Nov 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 02, 2018

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Classic or attenuated familial adenomatous polyposis Benign:1

Aug 15, 2023

All of Us Research Program, National Institutes of Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

APC-related disorder Benign:1

Sep 21, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hereditary cancer-predisposing syndrome Benign:1

Sep 30, 2017

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.8
DANN	Benign	0.63
PhyloP100		-0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs565688379; hg19: chr5-112178485;