rs2421943

chr10-92552058-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004969.4(IDE):c.99-14508C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,996 control chromosomes in the GnomAD database, including 12,001 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 0.37 (12001 hom., cov: 31)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IDE	NM_004969.4	c.99-14508C>T		intron_variant		ENST00000265986.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDE	ENST00000265986.11	c.99-14508C>T		intron_variant		1	NM_004969.4	P1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56914 AN: 151878 Hom.: 12003 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.375 AC: 56926 AN: 151996 Hom.: 12001 Cov.: 31 AF XY: 0.377 AC XY: 27999 AN XY: 74292

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.398

Alfa AF: 0.418 Hom.: 2832

Bravo AF: 0.361

Asia WGS AF: 0.540 AC: 1875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.5
Dann	Benign	0.22

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: rs2421943; hg19: chr10-94311815;