rs5786996

Variant names:

• chr10-92452778-T-TG
• rs5786996
• NM_004969.4:c.*1665dupC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004969.4(IDE):​c.*1665dupC variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0339 in 152,322 control chromosomes in the GnomAD database, including 137 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.034 (137 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IDE NM_004969.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDE	NM_004969.4	c.*1665dupC		3_prime_UTR_variant	Exon 25 of 25	ENST00000265986.11	NP_004960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDE	ENST00000265986.11	c.*1665dupC		3_prime_UTR_variant	Exon 25 of 25	1	NM_004969.4	ENSP00000265986.6

Frequencies

GnomAD3 genomes AF: 0.0340 AC: 5170 AN: 152204 Hom.: 137 Cov.: 32

Gnomad AFR AF: 0.00943

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0579

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.0398

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.0818

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0388

Gnomad OTH AF: 0.0210

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0339 AC: 5168 AN: 152322 Hom.: 137 Cov.: 32 AF XY: 0.0359 AC XY: 2675 AN XY: 74486

African (AFR) AF: 0.00940 AC: 391 AN: 41592

American (AMR) AF: 0.0578 AC: 884 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3468

East Asian (EAS) AF: 0.0395 AC: 205 AN: 5192

South Asian (SAS) AF: 0.0164 AC: 79 AN: 4822

European-Finnish (FIN) AF: 0.0818 AC: 868 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0388 AC: 2641 AN: 68028

Other (OTH) AF: 0.0208 AC: 44 AN: 2116

Alfa AF: 0.0396 Hom.: 14

Bravo AF: 0.0310

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs5786996; hg19: chr10-94212535;