rs7898493

Variant names:

• chr10-92535559-C-G
• rs7898493
• NM_004969.4:c.284-774G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004969.4(IDE):​c.284-774G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,202 control chromosomes in the GnomAD database, including 54,876 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 0.85 (54876 hom., cov: 32)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004969.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDE	NM_004969.4	MANE Select	c.284-774G>C		intron	N/A	NP_004960.2
	IDE	NM_001322793.2		c.284-774G>C		intron	N/A	NP_001309722.1
	IDE	NM_001322794.2		c.284-774G>C		intron	N/A	NP_001309723.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDE	ENST00000265986.11	TSL:1 MANE Select	c.284-774G>C		intron	N/A	ENSP00000265986.6
	IDE	ENST00000478361.6	TSL:1	n.*494-774G>C		intron	N/A	ENSP00000473506.1
	IDE	ENST00000650060.2		c.284-774G>C		intron	N/A	ENSP00000497272.1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128803 AN: 152084 Hom.: 54827 Cov.: 32

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.820

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

GnomAD4 genome AF: 0.847 AC: 128909 AN: 152202 Hom.: 54876 Cov.: 32 AF XY: 0.848 AC XY: 63073 AN XY: 74406

African (AFR) AF: 0.930 AC: 38638 AN: 41548

American (AMR) AF: 0.805 AC: 12310 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.854 AC: 2966 AN: 3472

East Asian (EAS) AF: 0.919 AC: 4757 AN: 5174

South Asian (SAS) AF: 0.837 AC: 4034 AN: 4822

European-Finnish (FIN) AF: 0.861 AC: 9105 AN: 10578

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.800 AC: 54366 AN: 67998

Other (OTH) AF: 0.819 AC: 1731 AN: 2114

Alfa AF: 0.827 Hom.: 6464

Bravo AF: 0.847

Asia WGS AF: 0.873 AC: 3036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.27
PhyloP100		-0.027
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: rs7898493; hg19: chr10-94295316;