Variant 5-112707473-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001407446.1(APC):c.-245A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 417,264 control chromosomes in the GnomAD database, including 681 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 329 hom., cov: 33)

Exomes 𝑓: 0.035 ( 352 hom. )

Consequence

APC
NM_001407446.1 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0670

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 5-112707473-A-C is Benign according to our data. Variant chr5-112707473-A-C is described in ClinVar as [Benign]. Clinvar id is 379248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
APC	NM_001407446.1 link	c.-245A>C	upstream_gene_variant	NP_001394375.1
APC	NM_001407447.1 link	c.-428A>C	upstream_gene_variant	NP_001394376.1
APC	NM_001407448.1 link	c.-195A>C	upstream_gene_variant	NP_001394377.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
APC	ENST00000509732.6 link	c.-195A>C	upstream_gene_variant	4	ENSP00000426541.2	D6RFL6
APC	ENST00000507379.6 link	c.-245A>C	upstream_gene_variant	2	ENSP00000423224.2	A0A2Q2SV78
APC	ENST00000505350.2 link	n.-245A>C	upstream_gene_variant	3	ENSP00000481752.1	A0A087WYF3

Frequencies

GnomAD3 genomes

AF:

0.0472

AC:

7180

AN:

152174

Hom.:

328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0237

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.134

Gnomad SAS

AF:

0.0697

Gnomad FIN

AF:

0.00489

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0173

Gnomad OTH

AF:

0.0592

GnomAD4 exome

AF:

0.0348

AC:

9219

AN:

264972

Hom.:

352

Cov.:

AF XY:

0.0367

AC XY:

5040

AN XY:

137444

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.0207

Gnomad4 ASJ exome

AF:

0.0341

Gnomad4 EAS exome

AF:

0.111

Gnomad4 SAS exome

AF:

0.0616

Gnomad4 FIN exome

AF:

0.00698

Gnomad4 NFE exome

AF:

0.0173

Gnomad4 OTH exome

AF:

0.0349

GnomAD4 genome

AF:

0.0472

AC:

7187

AN:

152292

Hom.:

329

Cov.:

AF XY:

0.0476

AC XY:

3542

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0236

Gnomad4 ASJ

AF:

0.0311

Gnomad4 EAS

AF:

0.134

Gnomad4 SAS

AF:

0.0695

Gnomad4 FIN

AF:

0.00489

Gnomad4 NFE

AF:

0.0173

Gnomad4 OTH

AF:

0.0586

Alfa

AF:

0.0320

Hom.:

Bravo

AF:

0.0519

Asia WGS

AF:

0.112

AC:

388

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 16, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Mar 04, 2025	- -

Familial adenomatous polyposis 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 04, 2025

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Jun 22, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.0

DANN

Benign

0.71

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