rs11187033

Positions:

• chr10-92502602-T-A
• chr10-92502602-T-G

Variant summary

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

The NM_004969.4(IDE):​c.1430+2192A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,130 control chromosomes in the GnomAD database, including 7,798 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 0.29 (7798 hom., cov: 32)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IDE	NM_004969.4	c.1430+2192A>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.1430+2192A>T		intron_variant		1	NM_004969.4	ENSP00000265986	P1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43724 AN: 152012 Hom.: 7803 Cov.: 32

Gnomad AFR AF: 0.0912

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.287 AC: 43717 AN: 152130 Hom.: 7798 Cov.: 32 AF XY: 0.293 AC XY: 21787 AN XY: 74344

Gnomad4 AFR AF: 0.0910

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.309

Alfa AF: 0.303 Hom.: 962

Bravo AF: 0.271

Asia WGS AF: 0.507 AC: 1761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.78

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: rs11187033; hg19: chr10-94262359;