5-112753783-T-C

Position:

• chr5-112753783-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.-18-1090T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,044 control chromosomes in the GnomAD database, including 33,620 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 (33620 hom., cov: 32)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: 0.465

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APC	NM_000038.6	c.-18-1090T>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.-18-1090T>C		intron_variant		5	NM_000038.6	ENSP00000257430.4

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100514 AN: 151926 Hom.: 33589 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.672

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.662 AC: 100602 AN: 152044 Hom.: 33620 Cov.: 32 AF XY: 0.661 AC XY: 49131 AN XY: 74316

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.668

Alfa AF: 0.640 Hom.: 45252

Bravo AF: 0.679

Asia WGS AF: 0.755 AC: 2622 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	-0.89
CADD	Benign	5.5
DANN	Benign	0.76

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: rs2439591; hg19: chr5-112089480;