rs11187033

Variant names:

• chr10-92502602-T-A
• rs11187033
• NM_004969.4:c.1430+2192A>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.82).
• 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 rank	MANE	Protein	UniProt
IDE	NM_004969.4	c.1430+2192A>T		intron_variant	Intron 11 of 24	ENST00000265986.11	NP_004960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDE	ENST00000265986.11	c.1430+2192A>T		intron_variant	Intron 11 of 24	1	NM_004969.4	ENSP00000265986.6

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

African (AFR) AF: 0.0910 AC: 3777 AN: 41528

American (AMR) AF: 0.261 AC: 3987 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3472

East Asian (EAS) AF: 0.672 AC: 3475 AN: 5170

South Asian (SAS) AF: 0.478 AC: 2307 AN: 4824

European-Finnish (FIN) AF: 0.389 AC: 4107 AN: 10558

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23679 AN: 67986

Other (OTH) AF: 0.309 AC: 653 AN: 2110

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
PhyloP100		1.5
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: rs11187033; hg19: chr10-94262359;