5-112778038-C-T

Position:

• chr5-112778038-C-T

Variant summary

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

The NM_000038.6(APC):​c.531+2301C>T variant causes a intron change. The variant allele was found at a frequency of 0.439 in 201,680 control chromosomes in the GnomAD database, including 22,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency:
  • Genomes: 𝑓 0.42 (15547 hom., cov: 33)
  • Exomes 𝑓: 0.51 (6761 hom.)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: 3.91

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APC	NM_000038.6	c.531+2301C>T		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+2301C>T		intron_variant		5	NM_000038.6	ENSP00000257430.4

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63209 AN: 151680 Hom.: 15549 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.454

GnomAD4 exome AF: 0.508 AC: 25333 AN: 49882 Hom.: 6761 Cov.: 0 AF XY: 0.495 AC XY: 14617 AN XY: 29508

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.668

Gnomad4 ASJ exome AF: 0.474

Gnomad4 EAS exome AF: 0.647

Gnomad4 SAS exome AF: 0.486

Gnomad4 FIN exome AF: 0.471

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.497

GnomAD4 genome AF: 0.416 AC: 63217 AN: 151798 Hom.: 15547 Cov.: 33 AF XY: 0.420 AC XY: 31180 AN XY: 74178

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.453

Alfa AF: 0.289 Hom.: 759

Bravo AF: 0.417

Asia WGS AF: 0.564 AC: 1958 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	-0.54
CADD	Benign	4.9
DANN	Benign	0.68

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: rs396321; hg19: chr5-112113735;