5-112707375-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001407446.1(APC):c.-343A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0704 in 339,774 control chromosomes in the GnomAD database, including 1,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.068 ( 490 hom., cov: 33)

Exomes 𝑓: 0.072 ( 632 hom. )

Consequence

APC
NM_001407446.1 upstream_gene

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.48

Publications

4 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: Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 5-112707375-A-G is Benign according to our data. Variant chr5-112707375-A-G is described in ClinVar as Benign. ClinVar VariationId is 386417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0953 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001407446.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
APC	NM_001407446.1	c.-343A>G	upstream_gene	N/A	NP_001394375.1
APC	NM_001407447.1	c.-526A>G	upstream_gene	N/A	NP_001394376.1	R4GMU6
APC	NM_001407448.1	c.-293A>G	upstream_gene	N/A	NP_001394377.1	R4GMU6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APC	ENST00000951167.1		c.-293A>G	upstream_gene	N/A	ENSP00000621226.1
APC	ENST00000509732.6	TSL:4	c.-293A>G	upstream_gene	N/A	ENSP00000426541.2	P25054-1
APC	ENST00000507379.6	TSL:2	c.-343A>G	upstream_gene	N/A	ENSP00000423224.2	P25054-3

Frequencies

GnomAD3 genomes

AF:

0.0679

AC:

10333

AN:

152282

Hom.:

487

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.0632

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0207

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0972

Gnomad OTH

AF:

0.0735

GnomAD4 exome

AF:

0.0724

AC:

13568

AN:

187374

Hom.:

632

AF XY:

0.0690

AC XY:

6585

AN XY:

95392

show subpopulations

African (AFR)

AF:

0.0181

AC:

123

AN:

6788

American (AMR)

AF:

0.0533

AC:

420

AN:

7886

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

721

AN:

7040

East Asian (EAS)

AF:

0.000200

AC:

AN:

14964

South Asian (SAS)

AF:

0.0264

AC:

631

AN:

23906

European-Finnish (FIN)

AF:

0.0843

AC:

521

AN:

6182

Middle Eastern (MID)

AF:

0.0919

AC:

AN:

860

European-Non Finnish (NFE)

AF:

0.0938

AC:

10133

AN:

107984

Other (OTH)

AF:

0.0796

AC:

937

AN:

11764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

607

1214

1820

2427

3034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.0679

AC:

10346

AN:

152400

Hom.:

490

Cov.:

AF XY:

0.0667

AC XY:

4968

AN XY:

74530

show subpopulations

African (AFR)

AF:

0.0178

AC:

740

AN:

41608

American (AMR)

AF:

0.0631

AC:

966

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

371

AN:

3472

East Asian (EAS)

AF:

0.000578

AC:

AN:

5194

South Asian (SAS)

AF:

0.0215

AC:

104

AN:

4834

European-Finnish (FIN)

AF:

0.115

AC:

1224

AN:

10626

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0972

AC:

6614

AN:

68032

Other (OTH)

AF:

0.0784

AC:

166

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

540

1080

1620

2160

2700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0625

Hom.:

161

Bravo

AF:

0.0634

Asia WGS

AF:

0.0420

AC:

145

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

APC-related disorder (1)

Familial adenomatous polyposis 1 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.24

(source)

DANN

Benign

0.70

PhyloP100

-1.5

PromoterAI

-0.040

Neutral

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over