rs5786996

Positions:

• chr10-92452778-T-TG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_004969.4(IDE):​c.*1665_*1666insC 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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IDE	NM_004969.4	c.*1665_*1666insC		3_prime_UTR_variant	25/25	ENST00000265986.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDE	ENST00000265986.11	c.*1665_*1666insC		3_prime_UTR_variant	25/25	1	NM_004969.4	P1

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

Gnomad4 NFE exome AF: 0.00

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

Gnomad4 AFR AF: 0.00940

Gnomad4 AMR AF: 0.0578

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.0395

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.0818

Gnomad4 NFE AF: 0.0388

Gnomad4 OTH AF: 0.0208

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs5786996; hg19: chr10-94212535;