rs138386816
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4BP6_Very_StrongBS1BS2
The NM_001407446.1(APC):c.-152C>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 0.00814 in 758,894 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0073 ( 6 hom., cov: 33)
Exomes 𝑓: 0.0084 ( 30 hom. )
Consequence
APC
NM_001407446.1 5_prime_UTR
NM_001407446.1 5_prime_UTR
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 2.78
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.11).
BP6
?
Variant 5-112707566-C-T is Benign according to our data. Variant chr5-112707566-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 469844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-112707566-C-T is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00728 (1109/152356) while in subpopulation SAS AF= 0.0101 (49/4832). AF 95% confidence interval is 0.00949. There are 6 homozygotes in gnomad4. There are 543 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1109 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APC | NM_001127511.3 | c.-152C>T | 5_prime_UTR_variant | 1/14 | |||
APC | NM_001354895.2 | c.-335C>T | 5_prime_UTR_variant | 1/16 | |||
APC | NM_001354897.2 | c.-152C>T | 5_prime_UTR_variant | 1/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APC | ENST00000507379.6 | c.-152C>T | 5_prime_UTR_variant | 1/14 | 2 | ||||
APC | ENST00000509732.6 | c.-102C>T | 5_prime_UTR_variant | 1/16 | 4 | P1 | |||
APC | ENST00000505350.2 | c.-152C>T | 5_prime_UTR_variant, NMD_transcript_variant | 1/16 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00730 AC: 1112AN: 152238Hom.: 6 Cov.: 33
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GnomAD4 exome AF: 0.00835 AC: 5066AN: 606538Hom.: 30 Cov.: 8 AF XY: 0.00824 AC XY: 2503AN XY: 303924
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GnomAD4 genome ? AF: 0.00728 AC: 1109AN: 152356Hom.: 6 Cov.: 33 AF XY: 0.00729 AC XY: 543AN XY: 74490
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 06, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Familial adenomatous polyposis 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | APC: BS1, BS2 - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at