chr5-112844212-C-A

Variant names:

• chr5-112844212-C-A
• rs1804197
• NM_000038.6:c.*86C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000038.6(APC):​c.*86C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0354 in 1,314,438 control chromosomes in the GnomAD database, including 2,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (812 hom., cov: 32)
  • Exomes 𝑓: 0.031 (1302 hom.)
• Consequence: APC NM_000038.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: 1.92
• Publications: 17 publications found

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

ENSG00000258864 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 5-112844212-C-A is Benign according to our data. Variant chr5-112844212-C-A is described in ClinVar as Benign. ClinVar VariationId is 83252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APC	NM_000038.6	c.*86C>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000257430.9	NP_000029.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000257430.9	c.*86C>A		3_prime_UTR_variant	Exon 16 of 16	5	NM_000038.6	ENSP00000257430.4
ENSG00000258864	ENST00000520401.1	n.229-12437C>A		intron_variant	Intron 3 of 7	3		ENSP00000454861.1

Frequencies

GnomAD3 genomes AF: 0.0719 AC: 10927 AN: 151998 Hom.: 813 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0763

Gnomad FIN AF: 0.00605

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0196

Gnomad OTH AF: 0.0783

GnomAD4 exome AF: 0.0306 AC: 35552 AN: 1162324 Hom.: 1302 Cov.: 16 AF XY: 0.0310 AC XY: 18134 AN XY: 584222

African (AFR) AF: 0.190 AC: 4762 AN: 25114

American (AMR) AF: 0.0266 AC: 742 AN: 27856

Ashkenazi Jewish (ASJ) AF: 0.0338 AC: 752 AN: 22228

East Asian (EAS) AF: 0.126 AC: 4418 AN: 35068

South Asian (SAS) AF: 0.0631 AC: 4379 AN: 69346

European-Finnish (FIN) AF: 0.00821 AC: 376 AN: 45806

Middle Eastern (MID) AF: 0.0617 AC: 311 AN: 5038

European-Non Finnish (NFE) AF: 0.0199 AC: 17551 AN: 882006

Other (OTH) AF: 0.0453 AC: 2261 AN: 49862

GnomAD4 genome AF: 0.0719 AC: 10937 AN: 152114 Hom.: 812 Cov.: 32 AF XY: 0.0720 AC XY: 5353 AN XY: 74374

African (AFR) AF: 0.182 AC: 7566 AN: 41460

American (AMR) AF: 0.0343 AC: 524 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3472

East Asian (EAS) AF: 0.152 AC: 788 AN: 5174

South Asian (SAS) AF: 0.0762 AC: 367 AN: 4816

European-Finnish (FIN) AF: 0.00605 AC: 64 AN: 10582

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0196 AC: 1336 AN: 68006

Other (OTH) AF: 0.0775 AC: 163 AN: 2104

Alfa AF: 0.0415 Hom.: 469

Bravo AF: 0.0802

Asia WGS AF: 0.136 AC: 471 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

APC-Associated Polyposis Disorders Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Familial adenomatous polyposis 1 Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24599579, 15122587) -

Familial colorectal cancer Other:1

-

Systems Biology Platform Zhejiang California International NanoSystems Institute

Significance: other

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1804197; hg19: chr5-112179909; COSMIC: COSV57326910;