10-92453329-TTA-TTATA

Variant names:

• chr10-92453329-T-TTA
• rs5786997
• NM_004969.4:c.*1113_*1114dupTA

Variant summary

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

The NM_004969.4(IDE):​c.*1113_*1114dupTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.068 in 152,256 control chromosomes in the GnomAD database, including 532 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.068 (532 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IDE NM_004969.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

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 (NFE) allele frequency at 95% confidence interval = 0.0979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDE	NM_004969.4	c.*1113_*1114dupTA		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	c.*1113_*1114dupTA		3_prime_UTR_variant	Exon 25 of 25	1	NM_004969.4	ENSP00000265986.6

Frequencies

GnomAD3 genomes AF: 0.0681 AC: 10361 AN: 152138 Hom.: 532 Cov.: 32

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.0525

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0929

Gnomad FIN AF: 0.0792

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0999

Gnomad OTH AF: 0.0679

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

GnomAD4 genome AF: 0.0680 AC: 10356 AN: 152256 Hom.: 532 Cov.: 32 AF XY: 0.0670 AC XY: 4989 AN XY: 74432

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.0525

Gnomad4 ASJ AF: 0.0704

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0922

Gnomad4 FIN AF: 0.0792

Gnomad4 NFE AF: 0.0999

Gnomad4 OTH AF: 0.0667

Bravo AF: 0.0645

Asia WGS AF: 0.0320 AC: 110 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5786997; hg19: chr10-94213086;