rs4705573

Positions:

• chr5-112724927-T-C

Variant summary

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

The NM_001407446.1(APC):​c.165+17045T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,056 control chromosomes in the GnomAD database, including 14,076 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 0.39 (14076 hom., cov: 31)
• Consequence: APC NM_001407446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APC	NM_001407446.1	c.165+17045T>C		intron_variant			NP_001394375.1
APC	NM_001407447.1	c.-19+17045T>C		intron_variant			NP_001394376.1
APC	NM_001407448.1	c.-19+17278T>C		intron_variant			NP_001394377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000509732.6	c.-19+17278T>C		intron_variant		4		ENSP00000426541.2
APC	ENST00000507379.6	c.165+17045T>C		intron_variant		2		ENSP00000423224.2
APC	ENST00000505350.2	n.165+17045T>C		intron_variant		3		ENSP00000481752.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59884 AN: 151938 Hom.: 14076 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.394 AC: 59889 AN: 152056 Hom.: 14076 Cov.: 31 AF XY: 0.397 AC XY: 29528 AN XY: 74314

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.429

Alfa AF: 0.414 Hom.: 1817

Bravo AF: 0.397

Asia WGS AF: 0.574 AC: 1995 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	6.8
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4705573; hg19: chr5-112060624;