rs372481703

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong

The NM_000038.6(APC):c.3512G>A(p.Arg1171His) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,613,912 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1171L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 1 hom. )

Consequence

APC
NM_000038.6 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.67

Publications

17 publications found

Variant links:

COSMIC-nc: COSV57363764

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09349775).

BP6

Variant 5-112839106-G-A is Benign according to our data. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112839106-G-A is described in CliVar as Likely_benign. Clinvar id is 418573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APC	NM_000038.6 link	c.3512G>A	p.Arg1171His	missense_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.3512G>A	p.Arg1171His	missense_variant	Exon 16 of 16	5	NM_000038.6	ENSP00000257430.4		P25054-1
ENSG00000258864	ENST00000520401.1 link	n.228+10134G>A		intron_variant	Intron 3 of 7	3		ENSP00000454861.1		H3BNH8

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000160

AC:

AN:

250310

AF XY:

0.00000738

show subpopulations

Gnomad AFR exome

AF:

0.000190

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:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000306

AC:

AN:

1111960

Other (OTH)

AF:

0.0000166

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome

Benign:3

Jul 10, 2018

Color Diagnostics, LLC DBA Color Health

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 28, 2021

Sema4, Sema4

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Jun 01, 2018

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. -

not specified

Benign:1

Nov 02, 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:1

Sep 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 07, 2023

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

May 14, 2024

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

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.36

T;T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.66

.;T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.093

T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

-0.90

N;N;.

PhyloP100

4.7

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.64

N;N;N

REVEL

Benign

0.26

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.46

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.17

MVP

0.55

ClinPred

0.050

GERP RS

5.6

Varity_R

0.034

gMVP

0.46

Mutation Taster

=95/5

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