GeneBe

10-92451547-C-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004969.4(IDE):​c.*2897G>C variant causes a downstream gene 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

IDE
NM_004969.4 downstream_gene

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.772

Publications

0 publications found
Variant links:
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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IDENM_004969.4 linkc.*2897G>C downstream_gene_variant ENST00000265986.11 NP_004960.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IDEENST00000265986.11 linkc.*2897G>C downstream_gene_variant 1 NM_004969.4 ENSP00000265986.6
IDEENST00000650060.2 linkc.*2897G>C downstream_gene_variant ENSP00000497272.1
IDEENST00000371581.9 linkc.*2897G>C downstream_gene_variant 2 ENSP00000360637.5
IDEENST00000679312.1 linkn.*4063G>C downstream_gene_variant ENSP00000504442.1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
624
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
340
African (AFR)
AF:
0.00
AC:
0
AN:
14
American (AMR)
AF:
0.00
AC:
0
AN:
4
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2
East Asian (EAS)
AF:
0.00
AC:
0
AN:
62
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
56
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
458
Other (OTH)
AF:
0.00
AC:
0
AN:
20
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.12
DANN
Benign
0.33
PhyloP100
-0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs2251101; hg19: chr10-94211304; API