chr10-92472490-T-C

Variant names:

• chr10-92472490-T-C
• rs2149632
• NM_004969.4:c.2117-2145A>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.2117-2145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,176 control chromosomes in the GnomAD database, including 7,847 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 (7847 hom., cov: 32)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 18 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 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.2117-2145A>G		intron	N/A	NP_004960.2
	IDE	NM_001322793.2		c.2117-2145A>G		intron	N/A	NP_001309722.1
	IDE	NM_001322794.2		c.2000-2145A>G		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.2117-2145A>G		intron	N/A	ENSP00000265986.6
	IDE	ENST00000650060.2		c.2117-2145A>G		intron	N/A	ENSP00000497272.1
	IDE	ENST00000676540.1		c.2117-2145A>G		intron	N/A	ENSP00000504633.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43864 AN: 152058 Hom.: 7851 Cov.: 32

Gnomad AFR AF: 0.0927

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.288 AC: 43861 AN: 152176 Hom.: 7847 Cov.: 32 AF XY: 0.294 AC XY: 21875 AN XY: 74390

African (AFR) AF: 0.0926 AC: 3845 AN: 41538

American (AMR) AF: 0.261 AC: 3988 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1192 AN: 3470

East Asian (EAS) AF: 0.672 AC: 3477 AN: 5174

South Asian (SAS) AF: 0.482 AC: 2325 AN: 4828

European-Finnish (FIN) AF: 0.389 AC: 4115 AN: 10570

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23723 AN: 68002

Other (OTH) AF: 0.310 AC: 654 AN: 2112

Alfa AF: 0.339 Hom.: 4830

Bravo AF: 0.272

Asia WGS AF: 0.511 AC: 1775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.66
PhyloP100		0.0070
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: rs2149632; hg19: chr10-94232247;