rs911239343

Variant names:

• chr5-112707443-A-C
• rs911239343
• NM_001407446.1:c.-275A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-112707443-A-C
• chr5-112707443-A-G
• chr5-112707443-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001407446.1(APC):​c.-275A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000391 in 255,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: APC NM_001407446.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291
• Publications: 0 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: Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001407446.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APC	NM_001407446.1		c.-275A>C		upstream_gene	N/A	NP_001394375.1
	APC	NM_001407447.1		c.-458A>C		upstream_gene	N/A	NP_001394376.1	R4GMU6
	APC	NM_001407448.1		c.-225A>C		upstream_gene	N/A	NP_001394377.1	R4GMU6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APC	ENST00000951167.1		c.-225A>C		upstream_gene	N/A	ENSP00000621226.1
	APC	ENST00000509732.6	TSL:4	c.-225A>C		upstream_gene	N/A	ENSP00000426541.2	P25054-1
	APC	ENST00000507379.6	TSL:2	c.-275A>C		upstream_gene	N/A	ENSP00000423224.2	P25054-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000391 AC: 1 AN: 255956 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 132408

African (AFR) AF: 0.00 AC: 0 AN: 8366

American (AMR) AF: 0.00 AC: 0 AN: 12156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8906

East Asian (EAS) AF: 0.00 AC: 0 AN: 18140

South Asian (SAS) AF: 0.0000263 AC: 1 AN: 37956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1084

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 145702

Other (OTH) AF: 0.00 AC: 0 AN: 15270

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.0
DANN	Benign	0.79
PhyloP100		0.29
PromoterAI		-0.088	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs911239343; hg19: chr5-112043140;