rs17875327

Variant names:

• chr10-92515052-A-G
• rs17875327
• NM_004969.4:c.662-10T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-92515052-A-G
• chr10-92515052-A-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.662-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 1,568,604 control chromosomes in the GnomAD database, including 7,869 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 0.072 (566 hom., cov: 32)
  • Exomes 𝑓: 0.094 (7303 hom.)
• Consequence: IDE NM_004969.4 intron
• Scores: Splicing: ADA: 0.3518
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 14 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=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDE	NM_004969.4	MANE Select	c.662-10T>C		intron	N/A	NP_004960.2	P14735-1
	IDE	NM_001322793.2		c.662-10T>C		intron	N/A	NP_001309722.1	A0A3B3ISG5
	IDE	NM_001322794.2		c.662-127T>C		intron	N/A	NP_001309723.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDE	ENST00000265986.11	TSL:1 MANE Select	c.662-10T>C		intron	N/A	ENSP00000265986.6	P14735-1
	IDE	ENST00000478361.6	TSL:1	n.*872-10T>C		intron	N/A	ENSP00000473506.1	R4GN65
	IDE	ENST00000971392.1		c.662-10T>C		intron	N/A	ENSP00000641451.1

Frequencies

GnomAD3 genomes AF: 0.0719 AC: 10928 AN: 152056 Hom.: 566 Cov.: 32

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0518

Gnomad ASJ AF: 0.0691

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0318

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0607

GnomAD2 exomes AF: 0.0805 AC: 18109 AN: 224962 AF XY: 0.0815

Gnomad AFR exome AF: 0.0156

Gnomad AMR exome AF: 0.0380

Gnomad ASJ exome AF: 0.0788

Gnomad EAS exome AF: 0.000295

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.0829

GnomAD4 exome AF: 0.0938 AC: 132923 AN: 1416428 Hom.: 7303 Cov.: 28 AF XY: 0.0926 AC XY: 65002 AN XY: 702312

African (AFR) AF: 0.0128 AC: 403 AN: 31600

American (AMR) AF: 0.0389 AC: 1402 AN: 36018

Ashkenazi Jewish (ASJ) AF: 0.0735 AC: 1789 AN: 24336

East Asian (EAS) AF: 0.000153 AC: 6 AN: 39144

South Asian (SAS) AF: 0.0303 AC: 2369 AN: 78198

European-Finnish (FIN) AF: 0.159 AC: 8390 AN: 52648

Middle Eastern (MID) AF: 0.0233 AC: 130 AN: 5572

European-Non Finnish (NFE) AF: 0.104 AC: 113910 AN: 1090444

Other (OTH) AF: 0.0774 AC: 4524 AN: 58468

GnomAD4 genome AF: 0.0718 AC: 10920 AN: 152176 Hom.: 566 Cov.: 32 AF XY: 0.0721 AC XY: 5363 AN XY: 74378

African (AFR) AF: 0.0157 AC: 653 AN: 41542

American (AMR) AF: 0.0516 AC: 789 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0691 AC: 240 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.0312 AC: 150 AN: 4812

European-Finnish (FIN) AF: 0.166 AC: 1750 AN: 10560

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7134 AN: 68000

Other (OTH) AF: 0.0601 AC: 127 AN: 2114

Alfa AF: 0.0786 Hom.: 281

Bravo AF: 0.0606

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.89
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.35
dbscSNV1_RF	Benign	0.40
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: rs17875327; hg19: chr10-94274809;