5-112778063-T-C

Position:

• chr5-112778063-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000038.6(APC):​c.531+2326T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 206,356 control chromosomes in the GnomAD database, including 46,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency:
  • Genomes: 𝑓 0.66 (33847 hom., cov: 33)
  • Exomes 𝑓: 0.67 (12413 hom.)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: 3.03

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APC	NM_000038.6	c.531+2326T>C		intron_variant		ENST00000257430.9	NP_000029.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000257430.9	c.531+2326T>C		intron_variant		5	NM_000038.6	ENSP00000257430	P1
CBX3P3	ENST00000508108.2	n.99A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100650 AN: 151714 Hom.: 33817 Cov.: 33

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.672

GnomAD4 exome AF: 0.670 AC: 36534 AN: 54524 Hom.: 12413 Cov.: 0 AF XY: 0.663 AC XY: 21231 AN XY: 32040

Gnomad4 AFR exome AF: 0.743

Gnomad4 AMR exome AF: 0.763

Gnomad4 ASJ exome AF: 0.614

Gnomad4 EAS exome AF: 0.914

Gnomad4 SAS exome AF: 0.726

Gnomad4 FIN exome AF: 0.576

Gnomad4 NFE exome AF: 0.631

Gnomad4 OTH exome AF: 0.650

GnomAD4 genome AF: 0.663 AC: 100736 AN: 151832 Hom.: 33847 Cov.: 33 AF XY: 0.663 AC XY: 49204 AN XY: 74184

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.901

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.668

Alfa AF: 0.639 Hom.: 3874

Bravo AF: 0.682

Asia WGS AF: 0.787 AC: 2735 AN: 3478

ClinVar

Significance: other

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Familial colorectal cancer Other:1

other, no assertion criteria provided

literature only

Systems Biology Platform Zhejiang California International NanoSystems Institute

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.2
DANN	Benign	0.51

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: rs401908; hg19: chr5-112113760;