10-92472490-T-C

Variant names:

• chr10-92472490-T-C
• rs2149632
• NM_004969.4:c.2117-2145A>G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDE	NM_004969.4	c.2117-2145A>G		intron_variant	Intron 17 of 24	ENST00000265986.11	NP_004960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDE	ENST00000265986.11	c.2117-2145A>G		intron_variant	Intron 17 of 24	1	NM_004969.4	ENSP00000265986.6

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

Gnomad4 AFR AF: 0.0926

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.310

Alfa AF: 0.341 Hom.: 4371

Bravo AF: 0.272

Asia WGS AF: 0.511 AC: 1775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs2149632; hg19: chr10-94232247;