10-92516769-A-T

Position:

• chr10-92516769-A-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IDE	NM_004969.4	c.662-1727T>A		intron_variant		ENST00000265986.11	NP_004960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IDE	ENST00000265986.11	c.662-1727T>A		intron_variant		1	NM_004969.4	ENSP00000265986.6

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

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.0518

Gnomad4 NFE AF: 0.0869

Gnomad4 OTH AF: 0.0943

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.78

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: rs7895832; hg19: chr10-94276526;