10-92516769-A-T

Variant names:

• chr10-92516769-A-T
• rs7895832
• NM_004969.4:c.662-1727T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004969.4(IDE):​c.662-1727T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,196 control chromosomes in the GnomAD database, including 882 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 0.10 (882 hom., cov: 32)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14
• Publications: 7 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 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.662-1727T>A		intron	N/A	NP_004960.2
	IDE	NM_001322793.2		c.662-1727T>A		intron	N/A	NP_001309722.1
	IDE	NM_001322794.2		c.662-1844T>A		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.662-1727T>A		intron	N/A	ENSP00000265986.6
	IDE	ENST00000478361.6	TSL:1	n.*872-1727T>A		intron	N/A	ENSP00000473506.1
	IDE	ENST00000971392.1		c.662-1727T>A		intron	N/A	ENSP00000641451.1

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15190 AN: 152078 Hom.: 876 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.0518

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0869

Gnomad OTH AF: 0.0924

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

GnomAD4 genome AF: 0.100 AC: 15230 AN: 152196 Hom.: 882 Cov.: 32 AF XY: 0.101 AC XY: 7540 AN XY: 74410

African (AFR) AF: 0.108 AC: 4487 AN: 41494

American (AMR) AF: 0.152 AC: 2318 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 180 AN: 3470

East Asian (EAS) AF: 0.141 AC: 731 AN: 5178

South Asian (SAS) AF: 0.171 AC: 826 AN: 4826

European-Finnish (FIN) AF: 0.0518 AC: 550 AN: 10620

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0869 AC: 5912 AN: 68010

Other (OTH) AF: 0.0943 AC: 199 AN: 2110

Alfa AF: 0.0963 Hom.: 94

Bravo AF: 0.107

Asia WGS AF: 0.136 AC: 473 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.78
PhyloP100		2.1
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: rs7895832; hg19: chr10-94276526;