rs10882066

Variant names:

• chr10-92464989-A-G
• rs10882066
• NM_004969.4:c.2488+687T>C

Variant summary

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

The NM_004969.4(IDE):​c.2488+687T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0952 in 152,184 control chromosomes in the GnomAD database, including 804 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 0.095 (804 hom., cov: 32)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004969.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDE	NM_004969.4	MANE Select	c.2488+687T>C		intron	N/A	NP_004960.2
	IDE	NM_001322793.2		c.2488+687T>C		intron	N/A	NP_001309722.1
	IDE	NM_001322794.2		c.2371+687T>C		intron	N/A	NP_001309723.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDE	ENST00000265986.11	TSL:1 MANE Select	c.2488+687T>C		intron	N/A	ENSP00000265986.6
	IDE	ENST00000650060.2		c.2488+687T>C		intron	N/A	ENSP00000497272.1
	IDE	ENST00000676540.1		c.2566+38T>C		intron	N/A	ENSP00000504633.1

Frequencies

GnomAD3 genomes AF: 0.0951 AC: 14465 AN: 152066 Hom.: 802 Cov.: 32

Gnomad AFR AF: 0.0939

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0519

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0865

Gnomad OTH AF: 0.0856

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

GnomAD4 genome AF: 0.0952 AC: 14488 AN: 152184 Hom.: 804 Cov.: 32 AF XY: 0.0963 AC XY: 7163 AN XY: 74402

African (AFR) AF: 0.0937 AC: 3889 AN: 41492

American (AMR) AF: 0.150 AC: 2294 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 180 AN: 3470

East Asian (EAS) AF: 0.127 AC: 655 AN: 5170

South Asian (SAS) AF: 0.170 AC: 822 AN: 4824

European-Finnish (FIN) AF: 0.0519 AC: 551 AN: 10616

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0865 AC: 5886 AN: 68012

Other (OTH) AF: 0.0875 AC: 184 AN: 2102

Alfa AF: 0.103 Hom.: 159

Bravo AF: 0.102

Asia WGS AF: 0.131 AC: 456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.4
DANN	Benign	0.30
PhyloP100		0.23
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: rs10882066; hg19: chr10-94224746;