5-112777830-A-C

Variant names:

• chr5-112777830-A-C
• rs467033
• NM_000038.6:c.531+2093A>C

Variant summary

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

The NM_000038.6(APC):​c.531+2093A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: APC NM_000038.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.950
• Publications: 9 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]

CBX3P3 (HGNC:42875): (CBX3 pseudogene 3)

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=-0.67).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000038.6. 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_000038.6	MANE Select	c.531+2093A>C		intron	N/A	NP_000029.2
	APC	NM_001407446.1		c.561+2093A>C		intron	N/A	NP_001394375.1
	APC	NM_001354896.2		c.531+2093A>C		intron	N/A	NP_001341825.1	R4GMU6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APC	ENST00000257430.9	TSL:5 MANE Select	c.531+2093A>C		intron	N/A	ENSP00000257430.4	P25054-1
	APC	ENST00000508376.6	TSL:1	c.531+2093A>C		intron	N/A	ENSP00000427089.2	P25054-1
	APC	ENST00000502371.3	TSL:1	n.531+2093A>C		intron	N/A	ENSP00000484935.2	A0A087X2F3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 92740 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 55554

African (AFR) AF: 0.00 AC: 0 AN: 2140

American (AMR) AF: 0.00 AC: 0 AN: 8708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1412

East Asian (EAS) AF: 0.00 AC: 0 AN: 4146

South Asian (SAS) AF: 0.00 AC: 0 AN: 9226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15750

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 574

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 47316

Other (OTH) AF: 0.00 AC: 0 AN: 3468

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 798

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.2
DANN	Benign	0.64
PhyloP100		0.95

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: rs467033; hg19: chr5-112113527;