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rs17875327

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

Scores

2
Splicing: ADA: 0.3518
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22
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 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
IDENM_004969.4 linkuse as main transcriptc.662-10T>C splice_polypyrimidine_tract_variant, intron_variant ENST00000265986.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IDEENST00000265986.11 linkuse as main transcriptc.662-10T>C splice_polypyrimidine_tract_variant, intron_variant 1 NM_004969.4 P1P14735-1

Frequencies

GnomAD3 genomes
AF:
0.0719
AC:
10928
AN:
152056
Hom.:
566
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0158
Gnomad AMI
AF:
0.0735
Gnomad AMR
AF:
0.0518
Gnomad ASJ
AF:
0.0691
Gnomad EAS
AF:
0.00154
Gnomad SAS
AF:
0.0318
Gnomad FIN
AF:
0.166
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.105
Gnomad OTH
AF:
0.0607
GnomAD3 exomes
AF:
0.0805
AC:
18109
AN:
224962
Hom.:
1020
AF XY:
0.0815
AC XY:
9921
AN XY:
121736
show subpopulations
Gnomad AFR exome
AF:
0.0156
Gnomad AMR exome
AF:
0.0380
Gnomad ASJ exome
AF:
0.0788
Gnomad EAS exome
AF:
0.000295
Gnomad SAS exome
AF:
0.0308
Gnomad FIN exome
AF:
0.165
Gnomad NFE exome
AF:
0.108
Gnomad OTH exome
AF:
0.0829
GnomAD4 exome
AF:
0.0938
AC:
132923
AN:
1416428
Hom.:
7303
Cov.:
28
AF XY:
0.0926
AC XY:
65002
AN XY:
702312
show subpopulations
Gnomad4 AFR exome
AF:
0.0128
Gnomad4 AMR exome
AF:
0.0389
Gnomad4 ASJ exome
AF:
0.0735
Gnomad4 EAS exome
AF:
0.000153
Gnomad4 SAS exome
AF:
0.0303
Gnomad4 FIN exome
AF:
0.159
Gnomad4 NFE exome
AF:
0.104
Gnomad4 OTH exome
AF:
0.0774
GnomAD4 genome
AF:
0.0718
AC:
10920
AN:
152176
Hom.:
566
Cov.:
32
AF XY:
0.0721
AC XY:
5363
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.0157
Gnomad4 AMR
AF:
0.0516
Gnomad4 ASJ
AF:
0.0691
Gnomad4 EAS
AF:
0.00154
Gnomad4 SAS
AF:
0.0312
Gnomad4 FIN
AF:
0.166
Gnomad4 NFE
AF:
0.105
Gnomad4 OTH
AF:
0.0601
Alfa
AF:
0.0788
Hom.:
195
Bravo
AF:
0.0606
Asia WGS
AF:
0.0180
AC:
62
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
CADD
Benign
17
DANN
Benign
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.35
dbscSNV1_RF
Benign
0.40
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs17875327; hg19: chr10-94274809; API