rs1178835678
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001407446.1(APC):c.-219C>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 0.0000493 in 445,898 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: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000058 ( 0 hom. )
Consequence
APC
NM_001407446.1 5_prime_UTR
NM_001407446.1 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.60
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 5-112707499-C-T is Benign according to our data. Variant chr5-112707499-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 469861.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APC | NM_001127511.3 | c.-219C>T | 5_prime_UTR_variant | 1/14 | |||
APC | NM_001354895.2 | c.-402C>T | 5_prime_UTR_variant | 1/16 | |||
APC | NM_001354897.2 | c.-219C>T | 5_prime_UTR_variant | 1/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APC | ENST00000507379.6 | upstream_gene_variant | 2 | ||||||
APC | ENST00000509732.6 | upstream_gene_variant | 4 | P1 | |||||
APC | ENST00000505350.2 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152270Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.0000579 AC: 17AN: 293510Hom.: 0 Cov.: 3 AF XY: 0.0000784 AC XY: 12AN XY: 153134
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152388Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74524
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial adenomatous polyposis 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Computational scores
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at