10-92490012-T-G

Variant names:

• chr10-92490012-T-G
• rs7093418
• NM_004969.4:c.1533+481A>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.1533+481A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 152,202 control chromosomes in the GnomAD database, including 55,252 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 (55252 hom., cov: 32)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDE	NM_004969.4	MANE Select	c.1533+481A>C		intron	N/A	NP_004960.2	P14735-1
	IDE	NM_001322793.2		c.1533+481A>C		intron	N/A	NP_001309722.1	A0A3B3ISG5
	IDE	NM_001322794.2		c.1416+481A>C		intron	N/A	NP_001309723.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDE	ENST00000265986.11	TSL:1 MANE Select	c.1533+481A>C		intron	N/A	ENSP00000265986.6	P14735-1
	IDE	ENST00000478361.6	TSL:1	n.*1743+481A>C		intron	N/A	ENSP00000473506.1	R4GN65
	IDE	ENST00000971392.1		c.1533+481A>C		intron	N/A	ENSP00000641451.1

Frequencies

GnomAD3 genomes AF: 0.850 AC: 129315 AN: 152084 Hom.: 55207 Cov.: 32

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.850 AC: 129418 AN: 152202 Hom.: 55252 Cov.: 32 AF XY: 0.851 AC XY: 63271 AN XY: 74388

African (AFR) AF: 0.918 AC: 38149 AN: 41538

American (AMR) AF: 0.814 AC: 12450 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3045 AN: 3470

East Asian (EAS) AF: 0.937 AC: 4851 AN: 5178

South Asian (SAS) AF: 0.839 AC: 4042 AN: 4820

European-Finnish (FIN) AF: 0.861 AC: 9116 AN: 10584

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.809 AC: 55005 AN: 68010

Other (OTH) AF: 0.824 AC: 1738 AN: 2110

Alfa AF: 0.828 Hom.: 12147

Bravo AF: 0.851

Asia WGS AF: 0.876 AC: 3046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.0
DANN	Benign	0.50
PhyloP100		-0.010
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: rs7093418; hg19: chr10-94249769;