rs1804197

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000258864 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id is 83252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112844212-C-A is described in Lovd as [Benign].
• 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

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.0266

Gnomad4 ASJ exome AF: 0.0338

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.0631

Gnomad4 FIN exome AF: 0.00821

Gnomad4 NFE exome AF: 0.0199

Gnomad4 OTH exome AF: 0.0453

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

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.0343

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.0762

Gnomad4 FIN AF: 0.00605

Gnomad4 NFE AF: 0.0196

Gnomad4 OTH AF: 0.0775

Alfa AF: 0.0309 Hom.: 140

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

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

LitVar

Other links and lift over

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