5-112778075-G-A

Position:

• chr5-112778075-G-A

Variant summary

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

The NM_000038.6(APC):​c.531+2338G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 207,008 control chromosomes in the GnomAD database, including 21,992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency:
  • Genomes: 𝑓 0.40 (14775 hom., cov: 33)
  • Exomes 𝑓: 0.50 (7217 hom.)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: 3.10

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]

CBX3P3 (HGNC:42875): (CBX3 pseudogene 3)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APC	NM_000038.6	c.531+2338G>A		intron_variant		ENST00000257430.9	NP_000029.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000257430.9	c.531+2338G>A		intron_variant		5	NM_000038.6	ENSP00000257430	P1
CBX3P3	ENST00000508108.2	n.87C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61028 AN: 151656 Hom.: 14777 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.497 AC: 27460 AN: 55234 Hom.: 7217 Cov.: 0 AF XY: 0.486 AC XY: 15810 AN XY: 32538

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.680

Gnomad4 ASJ exome AF: 0.482

Gnomad4 EAS exome AF: 0.664

Gnomad4 SAS exome AF: 0.489

Gnomad4 FIN exome AF: 0.422

Gnomad4 NFE exome AF: 0.477

Gnomad4 OTH exome AF: 0.485

GnomAD4 genome AF: 0.402 AC: 61029 AN: 151774 Hom.: 14775 Cov.: 33 AF XY: 0.405 AC XY: 30059 AN XY: 74162

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.441

Alfa AF: 0.427 Hom.: 1920

Bravo AF: 0.406

Asia WGS AF: 0.563 AC: 1956 AN: 3478

ClinVar

Significance: other

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Familial colorectal cancer Other:1

other, no assertion criteria provided

literature only

Systems Biology Platform Zhejiang California International NanoSystems Institute

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.6
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: rs414098; hg19: chr5-112113772;