5-112746227-A-G

Position:

• chr5-112746227-A-G

Variant summary

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

The NM_000038.6(APC):​c.-19+8302A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,976 control chromosomes in the GnomAD database, including 14,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency: Genomes: 𝑓 0.40 (14724 hom., cov: 32)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: 0.117

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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APC	NM_000038.6	c.-19+8302A>G		intron_variant		ENST00000257430.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APC	ENST00000257430.9	c.-19+8302A>G		intron_variant		5	NM_000038.6	P1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60914 AN: 151860 Hom.: 14726 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.401 AC: 60914 AN: 151976 Hom.: 14724 Cov.: 32 AF XY: 0.404 AC XY: 30050 AN XY: 74310

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.439

Alfa AF: 0.471 Hom.: 8281

Bravo AF: 0.404

Asia WGS AF: 0.565 AC: 1943 AN: 3442

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

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.3
DANN	Benign	0.90

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: rs6594646; hg19: chr5-112081924;