NM_004969.4:c.2965-284T>C

Variant names:

• chr10-92454823-A-G
• rs11187007
• NM_004969.4:c.2965-284T>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.2965-284T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,942 control chromosomes in the GnomAD database, including 7,927 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 0.29 (7927 hom., cov: 31)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 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.2965-284T>C		intron	N/A	NP_004960.2
	IDE	NM_001322793.2		c.2965-284T>C		intron	N/A	NP_001309722.1
	IDE	NM_001322794.2		c.2848-284T>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.2965-284T>C		intron	N/A	ENSP00000265986.6
	IDE	ENST00000971392.1		c.3106-284T>C		intron	N/A	ENSP00000641451.1
	IDE	ENST00000857320.1		c.3070-284T>C		intron	N/A	ENSP00000527379.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43637 AN: 151824 Hom.: 7929 Cov.: 31

Gnomad AFR AF: 0.0859

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.287 AC: 43635 AN: 151942 Hom.: 7927 Cov.: 31 AF XY: 0.294 AC XY: 21795 AN XY: 74232

African (AFR) AF: 0.0857 AC: 3558 AN: 41522

American (AMR) AF: 0.261 AC: 3981 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1190 AN: 3468

East Asian (EAS) AF: 0.709 AC: 3622 AN: 5106

South Asian (SAS) AF: 0.484 AC: 2329 AN: 4810

European-Finnish (FIN) AF: 0.390 AC: 4104 AN: 10532

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.348 AC: 23666 AN: 67930

Other (OTH) AF: 0.308 AC: 651 AN: 2112

Alfa AF: 0.269 Hom.: 2095

Bravo AF: 0.271

Asia WGS AF: 0.524 AC: 1820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.69
PhyloP100		-0.26
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: rs11187007; hg19: chr10-94214580;