Genetic Variant APC:n.22C>T (chr5-112707519-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NR_176365.1(APC):n.22C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000313 in 319,536 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000031 ( 0 hom. )

Consequence

APC
NR_176365.1 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.353

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: 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 5-112707519-C-T is Benign according to our data. Variant chr5-112707519-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1111220.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
APC	NR_176365.1 link	n.22C>T	non_coding_transcript_exon_variant	Exon 1 of 13
APC	NR_176366.1 link	n.22C>T	non_coding_transcript_exon_variant	Exon 1 of 14
APC	NM_001407446.1 link	c.-199C>T	5_prime_UTR_variant	Exon 1 of 16	NP_001394375.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
APC	ENST00000509732.6 link	c.-149C>T	5_prime_UTR_variant	Exon 1 of 16	4	ENSP00000426541.2	D6RFL6
APC	ENST00000507379.6 link	c.-199C>T	upstream_gene_variant		2	ENSP00000423224.2	A0A2Q2SV78
APC	ENST00000505350.2 link	n.-199C>T	upstream_gene_variant		3	ENSP00000481752.1	A0A087WYF3
APC	ENST00000713636.1 link	n.-382C>T	upstream_gene_variant			ENSP00000518937.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000313

AC:

AN:

319536

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

166454

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

9772

American (AMR)

AF:

0.00

AC:

AN:

14712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9870

East Asian (EAS)

AF:

0.00

AC:

AN:

19716

South Asian (SAS)

AF:

0.00

AC:

AN:

45736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1456

European-Non Finnish (NFE)

AF:

0.00000522

AC:

AN:

191622

Other (OTH)

AF:

0.00

AC:

AN:

17666

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial adenomatous polyposis 1

Benign:1

Jun 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

0.35

PromoterAI

-0.034

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over