rs11187059

Variant names:

• chr10-92538779-A-C
• rs11187059
• NM_004969.4:c.99-1229T>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.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
• Publications: 2 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=-0.91).
• 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 rank	MANE	Protein	UniProt
IDE	NM_004969.4	c.99-1229T>G		intron_variant	Intron 1 of 24	ENST00000265986.11	NP_004960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDE	ENST00000265986.11	c.99-1229T>G		intron_variant	Intron 1 of 24	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

African (AFR) AF: 0.220 AC: 4490 AN: 20382

American (AMR) AF: 0.308 AC: 2266 AN: 7360

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 187 AN: 1004

East Asian (EAS) AF: 0.351 AC: 639 AN: 1820

South Asian (SAS) AF: 0.348 AC: 793 AN: 2280

European-Finnish (FIN) AF: 0.192 AC: 498 AN: 2598

Middle Eastern (MID) AF: 0.133 AC: 13 AN: 98

European-Non Finnish (NFE) AF: 0.232 AC: 5902 AN: 25440

Other (OTH) AF: 0.218 AC: 190 AN: 872

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
PhyloP100		0.17
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: rs11187059; hg19: chr10-94298536; COSMIC: COSV56425763;