rs1999764

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004969.4(IDE):​c.98+13540A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,226 control chromosomes in the GnomAD database, including 924 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 0.10 ( 924 hom., cov: 31)

Consequence

IDE
NM_004969.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.221
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=-0.69).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IDENM_004969.4 linkuse as main transcriptc.98+13540A>G intron_variant ENST00000265986.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IDEENST00000265986.11 linkuse as main transcriptc.98+13540A>G intron_variant 1 NM_004969.4 P1P14735-1

Frequencies

GnomAD3 genomes
AF:
0.102
AC:
15504
AN:
152108
Hom.:
919
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.115
Gnomad AMI
AF:
0.0143
Gnomad AMR
AF:
0.153
Gnomad ASJ
AF:
0.0528
Gnomad EAS
AF:
0.126
Gnomad SAS
AF:
0.169
Gnomad FIN
AF:
0.0541
Gnomad MID
AF:
0.0443
Gnomad NFE
AF:
0.0877
Gnomad OTH
AF:
0.0918
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.102
AC:
15544
AN:
152226
Hom.:
924
Cov.:
31
AF XY:
0.103
AC XY:
7684
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.115
Gnomad4 AMR
AF:
0.153
Gnomad4 ASJ
AF:
0.0528
Gnomad4 EAS
AF:
0.127
Gnomad4 SAS
AF:
0.170
Gnomad4 FIN
AF:
0.0541
Gnomad4 NFE
AF:
0.0877
Gnomad4 OTH
AF:
0.0937
Alfa
AF:
0.0986
Hom.:
97
Bravo
AF:
0.109
Asia WGS
AF:
0.135
AC:
469
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
CADD
Benign
8.8
DANN
Benign
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1999764; hg19: chr10-94320139; API