rs2464805

Positions:

• chr5-112766096-C-A
• chr5-112766096-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000038.6(APC):​c.136-230C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,850 control chromosomes in the GnomAD database, including 33,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (33671 hom., cov: 31)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -1.11

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 5-112766096-C-A is Benign according to our data. Variant chr5-112766096-C-A is described in ClinVar as [Benign]. Clinvar id is 82871.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APC	NM_000038.6	c.136-230C>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.136-230C>A		intron_variant		5	NM_000038.6	ENSP00000257430	P1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100477 AN: 151732 Hom.: 33640 Cov.: 31

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.662 AC: 100563 AN: 151850 Hom.: 33671 Cov.: 31 AF XY: 0.662 AC XY: 49122 AN XY: 74194

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.667

Alfa AF: 0.635 Hom.: 28169

Bravo AF: 0.680

Asia WGS AF: 0.769 AC: 2664 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Familial colorectal cancer Other:1

other, no assertion criteria provided

literature only

Systems Biology Platform Zhejiang California International NanoSystems Institute

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- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.037
DANN	Benign	0.30

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: rs2464805; hg19: chr5-112101793;