rs2545162

chr5-112822734-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000038.6(APC):c.1408+743G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,012 control chromosomes in the GnomAD database, including 29,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.62 (29434 hom., cov: 32)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -0.0750

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-112822734-G-A is Benign according to our data. Variant chr5-112822734-G-A is described in ClinVar as [Benign]. Clinvar id is 83136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112822734-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APC	NM_000038.6	c.1408+743G>A		intron_variant		ENST00000257430.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APC	ENST00000257430.9	c.1408+743G>A		intron_variant		5	NM_000038.6	P1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93838 AN: 151894 Hom.: 29419 Cov.: 32

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.618 AC: 93908 AN: 152012 Hom.: 29434 Cov.: 32 AF XY: 0.619 AC XY: 45980 AN XY: 74286

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.632

Alfa AF: 0.639 Hom.: 30239

Bravo AF: 0.627

Asia WGS AF: 0.760 AC: 2641 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 13, 2022	- -

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	-0.84
Cadd	Benign	0.18
Dann	Benign	0.73

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: rs2545162; hg19: chr5-112158431;