10-92479610-AGTGTGTGTGTGT-AGTGTGTGTGT

Variant names:

• chr10-92479610-AGT-A
• rs3831274
• NM_004969.4:c.1740-191_1740-190delAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004969.4(IDE):​c.1740-191_1740-190delAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 454,762 control chromosomes in the GnomAD database, including 16,677 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (7656 hom., cov: 0)
  • Exomes 𝑓: 0.33 (9021 hom.)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481
• Publications: 1 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 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.1740-191_1740-190delAC		intron	N/A	NP_004960.2
	IDE	NM_001322793.2		c.1740-823_1740-822delAC		intron	N/A	NP_001309722.1
	IDE	NM_001322794.2		c.1623-191_1623-190delAC		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.1740-191_1740-190delAC		intron	N/A	ENSP00000265986.6
	IDE	ENST00000478361.6	TSL:1	n.*2074-191_*2074-190delAC		intron	N/A	ENSP00000473506.1
	IDE	ENST00000679069.1		n.3121_3122delAC		non_coding_transcript_exon	Exon 15 of 25

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43539 AN: 149960 Hom.: 7661 Cov.: 0

Gnomad AFR AF: 0.0953

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.328 AC: 99813 AN: 304706 Hom.: 9021 AF XY: 0.330 AC XY: 52547 AN XY: 159248

African (AFR) AF: 0.120 AC: 1123 AN: 9344

American (AMR) AF: 0.264 AC: 3582 AN: 13554

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 3234 AN: 9638

East Asian (EAS) AF: 0.519 AC: 11453 AN: 22080

South Asian (SAS) AF: 0.344 AC: 8887 AN: 25828

European-Finnish (FIN) AF: 0.347 AC: 7207 AN: 20776

Middle Eastern (MID) AF: 0.315 AC: 426 AN: 1352

European-Non Finnish (NFE) AF: 0.316 AC: 58028 AN: 183902

Other (OTH) AF: 0.322 AC: 5873 AN: 18232

GnomAD4 genome AF: 0.290 AC: 43535 AN: 150056 Hom.: 7656 Cov.: 0 AF XY: 0.296 AC XY: 21697 AN XY: 73204

African (AFR) AF: 0.0951 AC: 3906 AN: 41052

American (AMR) AF: 0.264 AC: 3971 AN: 15024

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1188 AN: 3406

East Asian (EAS) AF: 0.660 AC: 3397 AN: 5144

South Asian (SAS) AF: 0.481 AC: 2286 AN: 4752

European-Finnish (FIN) AF: 0.397 AC: 4017 AN: 10112

Middle Eastern (MID) AF: 0.316 AC: 91 AN: 288

European-Non Finnish (NFE) AF: 0.350 AC: 23583 AN: 67298

Other (OTH) AF: 0.312 AC: 647 AN: 2074

Alfa AF: 0.135 Hom.: 211

Bravo AF: 0.277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.48
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: rs3831274; hg19: chr10-94239367;