Genetic Variant APC:c.531+2093A>T (chr5-112777830-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

other no assertion criteria provided O:1

Conservation

PhyloP100: 0.950

Publications

9 publications found

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:

CBX3P3 (HGNC:42875): (CBX3 pseudogene 3)

CBX3P3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 link	c.531+2093A>T		intron_variant	Intron 5 of 15	ENST00000257430.9	NP_000029.2	P25054-1Q4LE70

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000257430.9 link	c.531+2093A>T		intron_variant	Intron 5 of 15	5	NM_000038.6	ENSP00000257430.4		P25054-1

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

62014

AN:

151922

Hom.:

15247

Cov.:

show subpopulations

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.:

AF XY:

0.469

AC XY:

25778

AN XY:

55008

show subpopulations

African (AFR)

AF:

0.115

AC:

246

AN:

2136

American (AMR)

AF:

0.695

AC:

6023

AN:

8672

Ashkenazi Jewish (ASJ)

AF:

0.462

AC:

649

AN:

1404

East Asian (EAS)

AF:

0.682

AC:

2792

AN:

4096

South Asian (SAS)

AF:

0.490

AC:

4481

AN:

9146

European-Finnish (FIN)

AF:

0.426

AC:

6664

AN:

15660

Middle Eastern (MID)

AF:

0.440

AC:

251

AN:

570

European-Non Finnish (NFE)

AF:

0.454

AC:

21266

AN:

46806

Other (OTH)

AF:

0.459

AC:

1583

AN:

3446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

857

1714

2571

3428

4285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

308

616

924

1232

1540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.408

AC:

62014

AN:

152040

Hom.:

15243

Cov.:

AF XY:

0.411

AC XY:

30544

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.129

AC:

5339

AN:

41518

American (AMR)

AF:

0.577

AC:

8819

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.514

AC:

1782

AN:

3466

East Asian (EAS)

AF:

0.656

AC:

3382

AN:

5152

South Asian (SAS)

AF:

0.551

AC:

2660

AN:

4824

European-Finnish (FIN)

AF:

0.415

AC:

4371

AN:

10544

Middle Eastern (MID)

AF:

0.459

AC:

135

AN:

294

European-Non Finnish (NFE)

AF:

0.502

AC:

34116

AN:

67930

Other (OTH)

AF:

0.447

AC:

944

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1628

3257

4885

6514

8142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

576

1152

1728

2304

2880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

LINK: link

Submissions by phenotype

Familial colorectal cancer

Other:1

Systems Biology Platform Zhejiang California International NanoSystems Institute

Significance:other

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.2

(source)

DANN

Benign

0.69

PhyloP100

0.95

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over