Variant 5-112766273-T-C 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.136-53T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 1,289,398 control chromosomes in the GnomAD database, including 2,123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 817 hom., cov: 32)

Exomes 𝑓: 0.032 ( 1306 hom. )

Consequence

APC
NM_000038.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 0.502

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 5-112766273-T-C is Benign according to our data. Variant chr5-112766273-T-C is described in ClinVar as [Benign]. Clinvar id is 82873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112766273-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 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.136-53T>C		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.136-53T>C		intron_variant		5	NM_000038.6	ENSP00000257430.4		P25054-1

Frequencies

GnomAD3 genomes

AF:

0.0725

AC:

11020

AN:

152104

Hom.:

817

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0411

Gnomad ASJ

AF:

0.0325

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.0683

Gnomad FIN

AF:

0.00584

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0206

Gnomad OTH

AF:

0.0803

GnomAD4 exome

AF:

0.0323

AC:

36771

AN:

1137176

Hom.:

1306

AF XY:

0.0326

AC XY:

18950

AN XY:

580898

show subpopulations

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.0366

Gnomad4 ASJ exome

AF:

0.0347

Gnomad4 EAS exome

AF:

0.118

Gnomad4 SAS exome

AF:

0.0596

Gnomad4 FIN exome

AF:

0.00876

Gnomad4 NFE exome

AF:

0.0208

Gnomad4 OTH exome

AF:

0.0451

GnomAD4 genome

AF:

0.0725

AC:

11030

AN:

152222

Hom.:

817

Cov.:

AF XY:

0.0723

AC XY:

5380

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.0412

Gnomad4 ASJ

AF:

0.0325

Gnomad4 EAS

AF:

0.137

Gnomad4 SAS

AF:

0.0681

Gnomad4 FIN

AF:

0.00584

Gnomad4 NFE

AF:

0.0206

Gnomad4 OTH

AF:

0.0795

Alfa

AF:

0.0367

Hom.:

204

Bravo

AF:

0.0819

Asia WGS

AF:

0.122

AC:

421

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, no assertion criteria provided

research

Mayo Clinic Laboratories, Mayo Clinic

- -

Familial adenomatous polyposis 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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

-0.75

CADD

Benign

DANN

Benign

0.86

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