rs2909786

chr5-112832368-A-Gchr5-112832368-A-T

Variant summary

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

The NM_000038.6(APC):c.1744-2583A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,972 control chromosomes in the GnomAD database, including 23,258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency: Genomes: 𝑓 0.55 (23258 hom., cov: 32)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: -0.239

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APC	NM_000038.6	c.1744-2583A>G		intron_variant		ENST00000257430.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APC	ENST00000257430.9	c.1744-2583A>G		intron_variant		5	NM_000038.6	P1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83009 AN: 151854 Hom.: 23245 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.547 AC: 83073 AN: 151972 Hom.: 23258 Cov.: 32 AF XY: 0.549 AC XY: 40760 AN XY: 74272

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.560

Alfa AF: 0.534 Hom.: 4466

Bravo AF: 0.560

Asia WGS AF: 0.722 AC: 2508 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	-0.91
Cadd	Benign	1.3
Dann	Benign	0.49

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: rs2909786; hg19: chr5-112168065;