5-112743085-A-G

Position:

• chr5-112743085-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+5160A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.053 in 152,256 control chromosomes in the GnomAD database, including 303 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 0.053 (303 hom., cov: 32)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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 (SAS) allele frequency at 95% confidence interval = 0.0814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APC	NM_000038.6	c.-19+5160A>G		intron_variant		ENST00000257430.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APC	ENST00000257430.9	c.-19+5160A>G		intron_variant		5	NM_000038.6	P1

Frequencies

GnomAD3 genomes AF: 0.0531 AC: 8073 AN: 152138 Hom.: 304 Cov.: 32

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0395

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0884

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0791

Gnomad OTH AF: 0.0521

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

GnomAD4 genome AF: 0.0530 AC: 8071 AN: 152256 Hom.: 303 Cov.: 32 AF XY: 0.0528 AC XY: 3932 AN XY: 74444

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.0396

Gnomad4 ASJ AF: 0.0513

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0883

Gnomad4 FIN AF: 0.0670

Gnomad4 NFE AF: 0.0790

Gnomad4 OTH AF: 0.0516

Alfa AF: 0.0754 Hom.: 253

Bravo AF: 0.0478

Asia WGS AF: 0.0290 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0040
DANN	Benign	0.20

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: rs1882619; hg19: chr5-112078782;