rs41116
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000038.6(APC):c.*1098T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 232,296 control chromosomes in the GnomAD database, including 26,028 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.40 ( 14803 hom., cov: 32)
Exomes 𝑓: 0.51 ( 11225 hom. )
Consequence
APC
NM_000038.6 3_prime_UTR
NM_000038.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.33
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 5-112845224-T-C is Benign according to our data. Variant chr5-112845224-T-C is described in ClinVar as [Benign]. Clinvar id is 83260.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APC | NM_000038.6 | c.*1098T>C | 3_prime_UTR_variant | 16/16 | ENST00000257430.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APC | ENST00000257430.9 | c.*1098T>C | 3_prime_UTR_variant | 16/16 | 5 | NM_000038.6 | P1 | ||
APC | ENST00000508376.6 | c.*1098T>C | 3_prime_UTR_variant | 17/17 | 1 | P1 | |||
APC | ENST00000509732.6 | c.*1098T>C | 3_prime_UTR_variant | 16/16 | 4 | P1 | |||
APC | ENST00000505350.2 | c.*9636T>C | 3_prime_UTR_variant, NMD_transcript_variant | 16/16 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.402 AC: 61122AN: 151964Hom.: 14805 Cov.: 32
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GnomAD4 exome AF: 0.513 AC: 41126AN: 80214Hom.: 11225 Cov.: 0 AF XY: 0.513 AC XY: 18959AN XY: 36942
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GnomAD4 genome ? AF: 0.402 AC: 61123AN: 152082Hom.: 14803 Cov.: 32 AF XY: 0.405 AC XY: 30138AN XY: 74334
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ClinVar
Significance: Benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
APC-Associated Polyposis Disorders Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Familial colorectal cancer Other:1
other, no assertion criteria provided | literature only | Systems Biology Platform Zhejiang California International NanoSystems Institute | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at