rs1057517554
Positions:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001407446.1(APC):c.-12T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 1,218,354 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 Uncertain significance (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000016 ( 0 hom. )
Consequence
APC
NM_001407446.1 5_prime_UTR
NM_001407446.1 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.50
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 Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APC | NM_001127511.3 | c.-12T>C | 5_prime_UTR_variant | 1/14 | |||
APC | NM_001354895.2 | c.-195T>C | 5_prime_UTR_variant | 1/16 | |||
APC | NM_001354897.2 | c.-12T>C | 5_prime_UTR_variant | 1/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APC | ENST00000507379.6 | c.-12T>C | 5_prime_UTR_variant | 1/14 | 2 | ||||
APC | ENST00000509732.6 | c.-19+57T>C | intron_variant | 4 | P1 | ||||
APC | ENST00000505350.2 | c.-12T>C | 5_prime_UTR_variant, NMD_transcript_variant | 1/16 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000732 AC: 1AN: 136668Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 74254
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GnomAD4 exome AF: 0.00000164 AC: 2AN: 1218354Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 595224
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GnomAD4 genome ? Cov.: 32
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32
Asia WGS
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3478
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial adenomatous polyposis 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Feb 19, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 07, 2024 | This variant occurs in a non-coding region of the APC gene. It does not change the encoded amino acid sequence of the APC protein. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 371825). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at