rs17875327
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_004969.4(IDE):c.662-10T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 1,568,604 control chromosomes in the GnomAD database, including 7,869 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.072 ( 566 hom., cov: 32)
Exomes 𝑓: 0.094 ( 7303 hom. )
Consequence
IDE
NM_004969.4 splice_polypyrimidine_tract, intron
NM_004969.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.3518
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.22
Genes affected
IDE (HGNC:5381): (insulin degrading enzyme) This gene encodes a zinc metallopeptidase that degrades intracellular insulin, and thereby terminates insulins activity, as well as participating in intercellular peptide signalling by degrading diverse peptides such as glucagon, amylin, bradykinin, and kallidin. The preferential affinity of this enzyme for insulin results in insulin-mediated inhibition of the degradation of other peptides such as beta-amyloid. Deficiencies in this protein's function are associated with Alzheimer's disease and type 2 diabetes mellitus but mutations in this gene have not been shown to be causitive for these diseases. This protein localizes primarily to the cytoplasm but in some cell types localizes to the extracellular space, cell membrane, peroxisome, and mitochondrion. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described but have not been experimentally verified.[provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IDE | NM_004969.4 | c.662-10T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000265986.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IDE | ENST00000265986.11 | c.662-10T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004969.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0719 AC: 10928AN: 152056Hom.: 566 Cov.: 32
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GnomAD3 exomes AF: 0.0805 AC: 18109AN: 224962Hom.: 1020 AF XY: 0.0815 AC XY: 9921AN XY: 121736
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GnomAD4 exome AF: 0.0938 AC: 132923AN: 1416428Hom.: 7303 Cov.: 28 AF XY: 0.0926 AC XY: 65002AN XY: 702312
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GnomAD4 genome ? AF: 0.0718 AC: 10920AN: 152176Hom.: 566 Cov.: 32 AF XY: 0.0721 AC XY: 5363AN XY: 74378
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at