5-112778063-T-C

Variant names:

• chr5-112778063-T-C
• rs401908
• NM_000038.6:c.531+2326T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000038.6(APC):​c.531+2326T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 206,356 control chromosomes in the GnomAD database, including 46,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency:
  • Genomes: 𝑓 0.66 (33847 hom., cov: 33)
  • Exomes 𝑓: 0.67 (12413 hom.)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: 3.03

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APC	NM_000038.6	c.531+2326T>C		intron_variant	Intron 5 of 15	ENST00000257430.9	NP_000029.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000257430.9	c.531+2326T>C		intron_variant	Intron 5 of 15	5	NM_000038.6	ENSP00000257430.4

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100650 AN: 151714 Hom.: 33817 Cov.: 33

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.672

GnomAD4 exome AF: 0.670 AC: 36534 AN: 54524 Hom.: 12413 Cov.: 0 AF XY: 0.663 AC XY: 21231 AN XY: 32040

Gnomad4 AFR exome AF: 0.743 AC: 1134 AN: 1526

Gnomad4 AMR exome AF: 0.763 AC: 5491 AN: 7194

Gnomad4 ASJ exome AF: 0.614 AC: 507 AN: 826

Gnomad4 EAS exome AF: 0.914 AC: 2648 AN: 2898

Gnomad4 SAS exome AF: 0.726 AC: 4166 AN: 5740

Gnomad4 FIN exome AF: 0.576 AC: 4002 AN: 6944

Gnomad4 NFE exome AF: 0.631 AC: 17222 AN: 27310

Gnomad4 Remaining exome AF: 0.650 AC: 1310 AN: 2014

GnomAD4 genome AF: 0.663 AC: 100736 AN: 151832 Hom.: 33847 Cov.: 33 AF XY: 0.663 AC XY: 49204 AN XY: 74184

Gnomad4 AFR AF: 0.705 AC: 0.705234 AN: 0.705234

Gnomad4 AMR AF: 0.706 AC: 0.706064 AN: 0.706064

Gnomad4 ASJ AF: 0.590 AC: 0.59041 AN: 0.59041

Gnomad4 EAS AF: 0.901 AC: 0.900931 AN: 0.900931

Gnomad4 SAS AF: 0.735 AC: 0.735002 AN: 0.735002

Gnomad4 FIN AF: 0.537 AC: 0.53722 AN: 0.53722

Gnomad4 NFE AF: 0.629 AC: 0.628856 AN: 0.628856

Gnomad4 OTH AF: 0.668 AC: 0.667773 AN: 0.667773

Alfa AF: 0.639 Hom.: 3874

Bravo AF: 0.682

Asia WGS AF: 0.787 AC: 2735 AN: 3478

ClinVar

Significance: other

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Familial colorectal cancer Other:1

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Systems Biology Platform Zhejiang California International NanoSystems Institute

Significance: other

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.2
DANN	Benign	0.51
Mutation Taster		=100/0	polymorphism (auto)

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: rs401908; hg19: chr5-112113760;