5-112738572-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000038.6(APC):c.-19+647A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 864,816 control chromosomes in the GnomAD database, including 103,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.40 ( 14756 hom., cov: 32)

Exomes 𝑓: 0.50 ( 88920 hom. )

Consequence

APC
NM_000038.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 0.408

Publications

8 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 Gene-Disease associations (from GenCC):

classic or attenuated familial adenomatous polyposis
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
desmoid tumor
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp
familial adenomatous polyposis 1
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
gastric adenocarcinoma and proximal polyposis of the stomach
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
sarcoma
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
APC-related attenuated familial adenomatous polyposis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Turcot syndrome with polyposis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Cenani-Lenz syndactyly syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

APC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 5-112738572-A-G is Benign according to our data. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-112738572-A-G is described in CliVar as Benign. Clinvar id is 82742.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APC	NM_000038.6 link	c.-19+647A>G		intron_variant	Intron 1 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.-19+647A>G		intron_variant	Intron 1 of 15	5	NM_000038.6	ENSP00000257430.4		P25054-1

Frequencies

GnomAD3 genomes

AF:

0.402

AC:

61025

AN:

151952

Hom.:

14751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.510

Gnomad AMR

AF:

0.568

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.667

Gnomad SAS

AF:

0.550

Gnomad FIN

AF:

0.411

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.492

Gnomad OTH

AF:

0.441

GnomAD4 exome

AF:

0.496

AC:

353236

AN:

712744

Hom.:

88920

AF XY:

0.496

AC XY:

164420

AN XY:

331398

show subpopulations

African (AFR)

AF:

0.0963

AC:

1274

AN:

13236

American (AMR)

AF:

0.593

AC:

490

AN:

826

Ashkenazi Jewish (ASJ)

AF:

0.471

AC:

2050

AN:

4354

East Asian (EAS)

AF:

0.666

AC:

2041

AN:

3064

South Asian (SAS)

AF:

0.538

AC:

7604

AN:

14122

European-Finnish (FIN)

AF:

0.471

AC:

128

AN:

272

Middle Eastern (MID)

AF:

0.426

AC:

591

AN:

1386

European-Non Finnish (NFE)

AF:

0.502

AC:

327606

AN:

652216

Other (OTH)

AF:

0.492

AC:

11452

AN:

23268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

8140

16279

24419

32558

40698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12996

25992

38988

51984

64980

<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:

0.401

AC:

61035

AN:

152072

Hom.:

14756

Cov.:

AF XY:

0.405

AC XY:

30092

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.127

AC:

5280

AN:

41514

American (AMR)

AF:

0.568

AC:

8683

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

1672

AN:

3466

East Asian (EAS)

AF:

0.667

AC:

3434

AN:

5152

South Asian (SAS)

AF:

0.550

AC:

2654

AN:

4824

European-Finnish (FIN)

AF:

0.411

AC:

4336

AN:

10562

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.492

AC:

33452

AN:

67958

Other (OTH)

AF:

0.440

AC:

930

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1659

3319

4978

6638

8297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.418

Hom.:

2018

Bravo

AF:

0.404

Asia WGS

AF:

0.569

AC:

1977

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 16, 2022

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.70

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

0.41

PromoterAI

-0.11

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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