Variant chr5-112780935-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000038.6(APC):c.645+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0837 in 1,372,594 control chromosomes in the GnomAD database, including 5,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 417 hom., cov: 32)

Exomes 𝑓: 0.086 ( 4959 hom. )

Consequence

APC
NM_000038.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.975

Variant links:

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]

APC links:

APC (HGNC:):

APC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 5-112780935-C-T is Benign according to our data. Variant chr5-112780935-C-T is described in ClinVar as [Benign]. Clinvar id is 218001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112780935-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APC	NM_000038.6 linkuse as main transcript	c.645+32C>T		intron_variant		ENST00000257430.9	NP_000029.2	P25054-1Q4LE70

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000257430.9 linkuse as main transcript	c.645+32C>T		intron_variant		5	NM_000038.6	ENSP00000257430.4		P25054-1

Frequencies

GnomAD3 genomes

AF:

0.0674

AC:

10248

AN:

151976

Hom.:

419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0319

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.0569

Gnomad ASJ

AF:

0.0686

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0909

Gnomad FIN

AF:

0.0695

Gnomad MID

AF:

0.131

Gnomad NFE

AF:

0.0934

Gnomad OTH

AF:

0.0685

GnomAD3 exomes

AF:

0.0757

AC:

16861

AN:

222672

Hom.:

790

AF XY:

0.0811

AC XY:

9721

AN XY:

119914

show subpopulations

Gnomad AFR exome

AF:

0.0300

Gnomad AMR exome

AF:

0.0391

Gnomad ASJ exome

AF:

0.0769

Gnomad EAS exome

AF:

0.000577

Gnomad SAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.0792

Gnomad NFE exome

AF:

0.0959

Gnomad OTH exome

AF:

0.0832

GnomAD4 exome

AF:

0.0857

AC:

104575

AN:

1220500

Hom.:

4959

Cov.:

AF XY:

0.0872

AC XY:

53800

AN XY:

616838

show subpopulations

Gnomad4 AFR exome

AF:

0.0307

Gnomad4 AMR exome

AF:

0.0411

Gnomad4 ASJ exome

AF:

0.0746

Gnomad4 EAS exome

AF:

0.000352

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.0793

Gnomad4 NFE exome

AF:

0.0923

Gnomad4 OTH exome

AF:

0.0809

GnomAD4 genome

AF:

0.0674

AC:

10257

AN:

152094

Hom.:

417

Cov.:

AF XY:

0.0669

AC XY:

4974

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0321

Gnomad4 AMR

AF:

0.0569

Gnomad4 ASJ

AF:

0.0686

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0906

Gnomad4 FIN

AF:

0.0695

Gnomad4 NFE

AF:

0.0934

Gnomad4 OTH

AF:

0.0673

Alfa

AF:

0.0854

Hom.:

113

Bravo

AF:

0.0639

Asia WGS

AF:

0.0310

AC:

110

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	research	Mayo Clinic Laboratories, Mayo Clinic	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 15, 2020	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Familial adenomatous polyposis 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.0

DANN

Benign

0.75

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over