rs10509645

Variant names:

• chr10-92518109-C-A
• rs10509645
• NM_004969.4:c.662-3067G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004969.4(IDE):​c.662-3067G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,696 control chromosomes in the GnomAD database, including 7,764 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 0.29 (7764 hom., cov: 30)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.436
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDE	NM_004969.4	c.662-3067G>T		intron_variant	Intron 4 of 24	ENST00000265986.11	NP_004960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDE	ENST00000265986.11	c.662-3067G>T		intron_variant	Intron 4 of 24	1	NM_004969.4	ENSP00000265986.6

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43521 AN: 151578 Hom.: 7769 Cov.: 30

Gnomad AFR AF: 0.0912

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.307

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.287 AC: 43514 AN: 151696 Hom.: 7764 Cov.: 30 AF XY: 0.292 AC XY: 21664 AN XY: 74080

African (AFR) AF: 0.0909 AC: 3769 AN: 41446

American (AMR) AF: 0.259 AC: 3936 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1184 AN: 3460

East Asian (EAS) AF: 0.671 AC: 3446 AN: 5132

South Asian (SAS) AF: 0.476 AC: 2286 AN: 4804

European-Finnish (FIN) AF: 0.388 AC: 4067 AN: 10474

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.348 AC: 23640 AN: 67888

Other (OTH) AF: 0.308 AC: 648 AN: 2104

Alfa AF: 0.297 Hom.: 1272

Bravo AF: 0.271

Asia WGS AF: 0.507 AC: 1760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.6
DANN	Benign	0.71
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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: rs10509645; hg19: chr10-94277866;