rs11187059

Positions:

• chr10-92538779-A-C

Variant summary

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

The NM_004969.4(IDE):​c.99-1229T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.24 (820 hom., cov: 0)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168

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 = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IDE	NM_004969.4	c.99-1229T>G		intron_variant		ENST00000265986.11	NP_004960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IDE	ENST00000265986.11	c.99-1229T>G		intron_variant		1	NM_004969.4	ENSP00000265986.6

Frequencies

GnomAD3 genomes AF: 0.241 AC: 14961 AN: 62010 Hom.: 817 Cov.: 0

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.242 AC: 14991 AN: 62062 Hom.: 820 Cov.: 0 AF XY: 0.245 AC XY: 7372 AN XY: 30038

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.218

Alfa AF: 0.127 Hom.: 64

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.3
DANN	Benign	0.82

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: rs11187059; hg19: chr10-94298536; COSMIC: COSV56425763;