5-112723897-A-G

Position:

• chr5-112723897-A-G

Variant summary

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

The NM_001407446.1(APC):​c.165+16015A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,848 control chromosomes in the GnomAD database, including 21,436 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 0.52 (21436 hom., cov: 31)
• Consequence: APC NM_001407446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APC	NM_001127511.3	c.165+16015A>G		intron_variant			NP_001120983.2
APC	NM_001354895.2	c.-19+16015A>G		intron_variant			NP_001341824.1
APC	NM_001354897.2	c.165+16015A>G		intron_variant			NP_001341826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000507379.6	c.165+16015A>G		intron_variant		2		ENSP00000423224
APC	ENST00000509732.6	c.-19+16248A>G		intron_variant		4		ENSP00000426541	P1
APC	ENST00000505350.2	c.165+16015A>G		intron_variant, NMD_transcript_variant		3		ENSP00000481752

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79557 AN: 151730 Hom.: 21426 Cov.: 31

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.524 AC: 79615 AN: 151848 Hom.: 21436 Cov.: 31 AF XY: 0.527 AC XY: 39112 AN XY: 74230

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.805

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.557

Alfa AF: 0.523 Hom.: 12224

Bravo AF: 0.538

Asia WGS AF: 0.710 AC: 2467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.92
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3846716; hg19: chr5-112059594;