rs1832196

Positions:

• chr10-92508577-G-A
• chr10-92508577-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004969.4(IDE):​c.1060+151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 507,410 control chromosomes in the GnomAD database, including 8,381 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 0.20 (3163 hom., cov: 29)
  • Exomes 𝑓: 0.15 (5218 hom.)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575

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]

IDE (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IDE	NM_004969.4	c.1060+151C>T		intron_variant		ENST00000265986.11	NP_004960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IDE	ENST00000265986.11	c.1060+151C>T		intron_variant		1	NM_004969.4	ENSP00000265986.6

Frequencies

GnomAD3 genomes AF: 0.196 AC: 28291 AN: 144474 Hom.: 3159 Cov.: 29

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.0702

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0700

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.149 AC: 54058 AN: 362918 Hom.: 5218 AF XY: 0.149 AC XY: 27963 AN XY: 187858

Gnomad4 AFR exome AF: 0.254

Gnomad4 AMR exome AF: 0.314

Gnomad4 ASJ exome AF: 0.0718

Gnomad4 EAS exome AF: 0.262

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.196 AC: 28316 AN: 144492 Hom.: 3163 Cov.: 29 AF XY: 0.197 AC XY: 13763 AN XY: 69902

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.0702

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.166

Alfa AF: 0.0256 Hom.: 18

Bravo AF: 0.207

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.16
DANN	Benign	0.56

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

Other links and lift over

dbSNP: rs1832196; hg19: chr10-94268334;