chr5-112843325-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_000038.6(APC):c.7731A>G(p.Ser2577Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,816 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 (★★). Synonymous variant affecting the same amino acid position (i.e. S2577S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

APC
NM_000038.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.569

Publications

1 publications found

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]

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

APC links:

ENSG00000258864 (HGNC:):

ENSG00000258864 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 5-112843325-A-G is Benign according to our data. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112843325-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 232288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.569 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APC	NM_000038.6 link	c.7731A>G	p.Ser2577Ser	synonymous_variant	Exon 16 of 16	ENST00000257430.9	NP_000029.2	P25054-1Q4LE70

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000257430.9 link	c.7731A>G	p.Ser2577Ser	synonymous_variant	Exon 16 of 16	5	NM_000038.6	ENSP00000257430.4		P25054-1
ENSG00000258864	ENST00000520401.1 link	n.229-13324A>G		intron_variant	Intron 3 of 7	3		ENSP00000454861.1		H3BNH8

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000478

GnomAD2 exomes

AF:

0.000132

AC:

AN:

250778

AF XY:

0.0000959

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000926

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:

0.000164

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461504

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727076

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.000827

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111706

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41566

American (AMR)

AF:

0.000196

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000107

Hom.:

Bravo

AF:

0.0000831

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jan 29, 2021

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2015

GeneDx

Significance: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. -

Nov 22, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:3

Jun 15, 2016

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. -

Aug 03, 2021

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Aug 06, 2016

Color Diagnostics, LLC DBA Color Health

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial adenomatous polyposis 1

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 10, 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. -

not provided

Benign:1

Jun 12, 2017

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Classic or attenuated familial adenomatous polyposis

Benign:1

Dec 01, 2023

All of Us Research Program, National Institutes of Health

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.7

(source)

DANN

Benign

0.69

PhyloP100

-0.57

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over