5-112707552-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP6

The NM_001407446.1(APC):c.-166C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 575,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

APC
NM_001407446.1 5_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.461

Publications

0 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: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 5-112707552-C-T is Benign according to our data. Variant chr5-112707552-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 469848.

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.-166C>T	5_prime_UTR	Exon 1 of 16	NP_001394375.1
APC	NM_001407447.1	c.-349C>T	5_prime_UTR	Exon 1 of 17	NP_001394376.1	R4GMU6
APC	NM_001407448.1	c.-116C>T	5_prime_UTR	Exon 1 of 17	NP_001394377.1	R4GMU6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APC	ENST00000951167.1		c.-116C>T	5_prime_UTR	Exon 1 of 17	ENSP00000621226.1
APC	ENST00000509732.6	TSL:4	c.-116C>T	5_prime_UTR	Exon 1 of 16	ENSP00000426541.2	P25054-1
APC	ENST00000507379.6	TSL:2	c.-166C>T	5_prime_UTR	Exon 1 of 14	ENSP00000423224.2	P25054-3

Frequencies

GnomAD3 genomes

AF:

0.000374

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.0000426

AC:

AN:

422718

Hom.:

Cov.:

AF XY:

0.0000369

AC XY:

AN XY:

216854

show subpopulations

African (AFR)

AF:

0.000919

AC:

AN:

11968

American (AMR)

AF:

0.00

AC:

AN:

17894

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11004

East Asian (EAS)

AF:

0.00

AC:

AN:

19962

South Asian (SAS)

AF:

0.00

AC:

AN:

49724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2092

European-Non Finnish (NFE)

AF:

0.0000107

AC:

AN:

279526

Other (OTH)

AF:

0.000189

AC:

AN:

21122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000374

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

41590

American (AMR)

AF:

0.000131

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68028

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.000366

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial adenomatous polyposis 1 (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

0.46

PromoterAI

0.14

Neutral

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over