chr5-112751630-T-G

Position:

• chr5-112751630-T-G

Variant summary

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

The NM_000038.6(APC):​c.-18-3243T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,662 control chromosomes in the GnomAD database, including 22,957 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency: Genomes: 𝑓 0.54 (22957 hom., cov: 32)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: -0.604

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APC	NM_000038.6	c.-18-3243T>G		intron_variant		ENST00000257430.9	NP_000029.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000257430.9	c.-18-3243T>G		intron_variant		5	NM_000038.6	ENSP00000257430.4

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82434 AN: 151544 Hom.: 22945 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.544 AC: 82492 AN: 151662 Hom.: 22957 Cov.: 32 AF XY: 0.546 AC XY: 40464 AN XY: 74116

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.575

Alfa AF: 0.553 Hom.: 35302

Bravo AF: 0.559

Asia WGS AF: 0.714 AC: 2460 AN: 3450

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	-0.98
CADD	Benign	1.4
DANN	Benign	0.62

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: rs11954856; hg19: chr5-112087327;