rs1278244063

Variant names:

• chr5-112707551-G-A
• rs1278244063
• ENST00000505350.2:n.-167G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-112707551-G-A
• chr5-112707551-G-C
• chr5-112707551-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000505350.2(APC):​n.-167G>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.0000123 in 570,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: APC ENST00000505350.2 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 3.64
• 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: 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000505350.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APC	NR_176365.1		n.54G>A		non_coding_transcript_exon	Exon 1 of 13
	APC	NR_176366.1		n.54G>A		non_coding_transcript_exon	Exon 1 of 14
	APC	NM_001407446.1		c.-167G>A		5_prime_UTR	Exon 1 of 16	NP_001394375.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APC	ENST00000505350.2	TSL:3	n.-167G>A		non_coding_transcript_exon	Exon 1 of 16	ENSP00000481752.1
	APC	ENST00000509732.6	TSL:4	c.-117G>A		5_prime_UTR	Exon 1 of 16	ENSP00000426541.2
	APC	ENST00000507379.6	TSL:2	c.-167G>A		5_prime_UTR	Exon 1 of 14	ENSP00000423224.2

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152276 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000964

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 2 AN: 417864 Hom.: 0 Cov.: 6 AF XY: 0.00000466 AC XY: 1 AN XY: 214506

African (AFR) AF: 0.00 AC: 0 AN: 11912

American (AMR) AF: 0.00 AC: 0 AN: 17934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11002

East Asian (EAS) AF: 0.00 AC: 0 AN: 19956

South Asian (SAS) AF: 0.00 AC: 0 AN: 49658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2066

European-Non Finnish (NFE) AF: 0.00000728 AC: 2 AN: 274900

Other (OTH) AF: 0.00 AC: 0 AN: 20988

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152276 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74396

African (AFR) AF: 0.0000964 AC: 4 AN: 41478

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Familial adenomatous polyposis 1 (1)
-	1	-	Gastric cancer;C0346629:Colorectal cancer;C1851124:Desmoid disease, hereditary;C2239176:Hepatocellular carcinoma;C2713442:Familial adenomatous polyposis 1;C4749917:Gastric adenocarcinoma and proximal polyposis of the stomach (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Benign	0.94
PhyloP100		3.6
PromoterAI		0.15	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1278244063; hg19: chr5-112043248;