5-112707477-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001407446.1(APC):c.-241A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 419,674 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00074 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 15 hom. )

Consequence

APC
NM_001407446.1 upstream_gene

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.19

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 5-112707477-A-G is Benign according to our data. Variant chr5-112707477-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 469868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000737 (110/149294) while in subpopulation SAS AF= 0.00828 (40/4832). AF 95% confidence interval is 0.00625. There are 1 homozygotes in gnomad4. There are 56 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 110 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
APC	NM_001407446.1 link	c.-241A>G	upstream_gene_variant	NP_001394375.1
APC	NM_001407447.1 link	c.-424A>G	upstream_gene_variant	NP_001394376.1
APC	NM_001407448.1 link	c.-191A>G	upstream_gene_variant	NP_001394377.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
APC	ENST00000509732.6 link	c.-191A>G	upstream_gene_variant	4	ENSP00000426541.2	D6RFL6
APC	ENST00000507379.6 link	c.-241A>G	upstream_gene_variant	2	ENSP00000423224.2	A0A2Q2SV78
APC	ENST00000505350.2 link	n.-241A>G	upstream_gene_variant	3	ENSP00000481752.1	A0A087WYF3

Frequencies

GnomAD3 genomes

AF:

0.000737

AC:

110

AN:

149182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000778

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00210

AC:

568

AN:

270380

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

417

AN XY:

140446

show subpopulations

Gnomad4 AFR exome

AF:

0.000248

Gnomad4 AMR exome

AF:

0.0000787

Gnomad4 ASJ exome

AF:

0.000108

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0114

Gnomad4 FIN exome

AF:

0.000117

Gnomad4 NFE exome

AF:

0.000553

Gnomad4 OTH exome

AF:

0.000571

GnomAD4 genome

AF:

0.000737

AC:

110

AN:

149294

Hom.:

Cov.:

AF XY:

0.000767

AC XY:

AN XY:

73022

show subpopulations

Gnomad4 AFR

AF:

0.0000775

Gnomad4 AMR

AF:

0.000198

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000941

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000268

Hom.:

Bravo

AF:

0.000453

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

APC: BS1 -

APC-related disorder

Benign:1

Oct 20, 2023

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.73

DANN

Benign

0.45

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over