5-112777830-A-T

Variant names:

• chr5-112777830-A-T
• rs467033
• NM_000038.6:c.531+2093A>T

Variant summary

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

The NM_000038.6(APC):​c.531+2093A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 243,976 control chromosomes in the GnomAD database, including 26,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency:
  • Genomes: 𝑓 0.41 (15243 hom., cov: 32)
  • Exomes 𝑓: 0.48 (11252 hom.)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: 0.950

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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APC	NM_000038.6	c.531+2093A>T		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+2093A>T		intron_variant	Intron 5 of 15	5	NM_000038.6	ENSP00000257430.4

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62014 AN: 151922 Hom.: 15247 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.448

GnomAD4 exome AF: 0.478 AC: 43955 AN: 91936 Hom.: 11252 Cov.: 0 AF XY: 0.469 AC XY: 25778 AN XY: 55008

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.695

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.682

Gnomad4 SAS exome AF: 0.490

Gnomad4 FIN exome AF: 0.426

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.459

GnomAD4 genome AF: 0.408 AC: 62014 AN: 152040 Hom.: 15243 Cov.: 32 AF XY: 0.411 AC XY: 30544 AN XY: 74300

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.447

Alfa AF: 0.296 Hom.: 798

Bravo AF: 0.411

Asia WGS AF: 0.568 AC: 1971 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	-0.67
CADD	Benign	6.2
DANN	Benign	0.69

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: rs467033; hg19: chr5-112113527;