10-92465260-G-C

Variant names:

• chr10-92465260-G-C
• rs7899603
• NM_004969.4:c.2488+416C>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.2488+416C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,010 control chromosomes in the GnomAD database, including 18,031 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 0.47 (18031 hom., cov: 31)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDE	NM_004969.4	c.2488+416C>G		intron_variant	Intron 20 of 24	ENST00000265986.11	NP_004960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDE	ENST00000265986.11	c.2488+416C>G		intron_variant	Intron 20 of 24	1	NM_004969.4	ENSP00000265986.6

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71718 AN: 151892 Hom.: 18008 Cov.: 31

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.472 AC: 71791 AN: 152010 Hom.: 18031 Cov.: 31 AF XY: 0.472 AC XY: 35070 AN XY: 74314

African (AFR) AF: 0.642 AC: 26605 AN: 41432

American (AMR) AF: 0.483 AC: 7378 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1140 AN: 3468

East Asian (EAS) AF: 0.248 AC: 1283 AN: 5164

South Asian (SAS) AF: 0.329 AC: 1586 AN: 4822

European-Finnish (FIN) AF: 0.461 AC: 4872 AN: 10570

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27650 AN: 67972

Other (OTH) AF: 0.419 AC: 886 AN: 2114

Alfa AF: 0.294 Hom.: 697

Bravo AF: 0.478

Asia WGS AF: 0.340 AC: 1183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.51
PhyloP100		-0.23
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: rs7899603; hg19: chr10-94225017;