rs2431507

chr5-112810484-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.835-5011A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 152,296 control chromosomes in the GnomAD database, including 615 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 0.084 (615 hom., cov: 32)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APC	NM_000038.6	c.835-5011A>G		intron_variant		ENST00000257430.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APC	ENST00000257430.9	c.835-5011A>G		intron_variant		5	NM_000038.6	P1

Frequencies

GnomAD3 genomes AF: 0.0841 AC: 12799 AN: 152178 Hom.: 617 Cov.: 32

Gnomad AFR AF: 0.0649

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0936

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0808

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

GnomAD4 genome AF: 0.0841 AC: 12809 AN: 152296 Hom.: 615 Cov.: 32 AF XY: 0.0846 AC XY: 6301 AN XY: 74470

Gnomad4 AFR AF: 0.0650

Gnomad4 AMR AF: 0.0666

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0935

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0795

Alfa AF: 0.0969 Hom.: 117

Bravo AF: 0.0785

Asia WGS AF: 0.0340 AC: 119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.1
Dann	Benign	0.58

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: rs2431507; hg19: chr5-112146181;