5-112840730-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_000038.6(APC):c.5136A>G(p.Glu1712Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,150 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

APC
NM_000038.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.109

Publications

0 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 -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 5-112840730-A-G is Benign according to our data. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112840730-A-G is described in CliVar as Benign/Likely_benign. Clinvar id is 469992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.109 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APC	NM_000038.6 link	c.5136A>G	p.Glu1712Glu	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.5136A>G	p.Glu1712Glu	synonymous_variant	Exon 16 of 16	5	NM_000038.6	ENSP00000257430.4		P25054-1
ENSG00000258864	ENST00000520401.1 link	n.228+11758A>G		intron_variant	Intron 3 of 7	3		ENSP00000454861.1		H3BNH8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

AN:

250100

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111978

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74500

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000240

AC:

AN:

41586

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

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:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2110

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial adenomatous polyposis 1

Benign:2

Feb 18, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 01, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.6

(source)

DANN

Benign

0.72

PhyloP100

-0.11

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over