rs17107721

Positions:

• chr10-92538743-G-A
• chr10-92538743-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004969.4(IDE):​c.99-1193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0435 in 148,152 control chromosomes in the GnomAD database, including 167 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 0.044 (167 hom., cov: 31)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0435 (6447/148152) while in subpopulation AFR AF= 0.0475 (1914/40282). AF 95% confidence interval is 0.0457. There are 167 homozygotes in gnomad4. There are 2994 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 167 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IDE	NM_004969.4	c.99-1193C>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.99-1193C>T		intron_variant		1	NM_004969.4	ENSP00000265986	P1

Frequencies

GnomAD3 genomes AF: 0.0435 AC: 6442 AN: 148048 Hom.: 168 Cov.: 31

Gnomad AFR AF: 0.0474

Gnomad AMI AF: 0.00996

Gnomad AMR AF: 0.0445

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.00121

Gnomad SAS AF: 0.0309

Gnomad FIN AF: 0.00895

Gnomad MID AF: 0.0833

Gnomad NFE AF: 0.0428

Gnomad OTH AF: 0.0575

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

GnomAD4 genome AF: 0.0435 AC: 6447 AN: 148152 Hom.: 167 Cov.: 31 AF XY: 0.0416 AC XY: 2994 AN XY: 71910

Gnomad4 AFR AF: 0.0475

Gnomad4 AMR AF: 0.0444

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.00121

Gnomad4 SAS AF: 0.0306

Gnomad4 FIN AF: 0.00895

Gnomad4 NFE AF: 0.0429

Gnomad4 OTH AF: 0.0569

Alfa AF: 0.0112 Hom.: 4

Bravo AF: 0.0468

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs17107721; hg19: chr10-94298500;