rs13167522

chr5-112831611-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.1743+2639T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0601 in 152,254 control chromosomes in the GnomAD database, including 392 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.060 (392 hom., cov: 32)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

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 (NFE) allele frequency at 95% confidence interval = 0.0884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APC	NM_000038.6	c.1743+2639T>C		intron_variant		ENST00000257430.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APC	ENST00000257430.9	c.1743+2639T>C		intron_variant		5	NM_000038.6	P1

Frequencies

GnomAD3 genomes AF: 0.0602 AC: 9156 AN: 152136 Hom.: 392 Cov.: 32

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.0746

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0902

Gnomad OTH AF: 0.0630

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

GnomAD4 genome AF: 0.0601 AC: 9156 AN: 152254 Hom.: 392 Cov.: 32 AF XY: 0.0576 AC XY: 4290 AN XY: 74434

Gnomad4 AFR AF: 0.0165

Gnomad4 AMR AF: 0.0563

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.0746

Gnomad4 NFE AF: 0.0903

Gnomad4 OTH AF: 0.0624

Alfa AF: 0.0758 Hom.: 108

Bravo AF: 0.0583

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	9.0
Dann	Benign	0.69

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: rs13167522; hg19: chr5-112167308;