rs375254915
Positions:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_000038.6(APC):c.532-14A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
Consequence
APC
NM_000038.6 splice_polypyrimidine_tract, intron
NM_000038.6 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.376
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.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 5-112780776-A-G is Benign according to our data. Variant chr5-112780776-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1626231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APC | NM_000038.6 | c.532-14A>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000257430.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APC | ENST00000257430.9 | c.532-14A>G | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_000038.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000410 AC: 1AN: 243970Hom.: 0 AF XY: 0.00000757 AC XY: 1AN XY: 132050
GnomAD3 exomes
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1
AN:
243970
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AC XY:
1
AN XY:
132050
Gnomad AFR exome
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GnomAD4 exome Cov.: 25
GnomAD4 exome
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25
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Bravo
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial adenomatous polyposis 1 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Feb 23, 2024 | This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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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