5-112820096-G-C

Position:

• chr5-112820096-G-C

Variant summary

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

The NM_000038.6(APC):​c.1312+752G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 151,650 control chromosomes in the GnomAD database, including 28,470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency: Genomes: 𝑓 0.61 (28470 hom., cov: 29)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: 1.20

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APC	NM_000038.6	c.1312+752G>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.1312+752G>C		intron_variant		5	NM_000038.6	ENSP00000257430.4

Frequencies

GnomAD3 genomes AF: 0.606 AC: 91873 AN: 151532 Hom.: 28453 Cov.: 29

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.606 AC: 91941 AN: 151650 Hom.: 28470 Cov.: 29 AF XY: 0.608 AC XY: 45037 AN XY: 74090

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.904

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.615

Alfa AF: 0.465 Hom.: 1222

Bravo AF: 0.615

Asia WGS AF: 0.775 AC: 2692 AN: 3476

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	-0.88
CADD	Benign	9.3
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs501250; hg19: chr5-112155793;