Genetic Variant IDE:c.*2897G>A (chr10-92451547-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004969.4(IDE):c.*2897G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,738 control chromosomes in the GnomAD database, including 47,239 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 0.78 ( 47089 hom., cov: 31)

Exomes 𝑓: 0.68 ( 150 hom. )

Consequence

IDE
NM_004969.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.772

Variant links:

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]

IDE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDE	NM_004969.4 link	c.*2897G>A		downstream_gene_variant		ENST00000265986.11	NP_004960.2	P14735-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
IDE	ENST00000265986.11 link	c.*2897G>A	downstream_gene_variant	1	NM_004969.4	ENSP00000265986.6	P14735-1
IDE	ENST00000650060.2 link	c.*2897G>A	downstream_gene_variant			ENSP00000497272.1	A0A3B3ISG5
IDE	ENST00000371581.9 link	c.*2897G>A	downstream_gene_variant	2		ENSP00000360637.5	P14735-2
IDE	ENST00000679312.1 link	n.*4063G>A	downstream_gene_variant			ENSP00000504442.1	A0A7I2YQS6

Frequencies

GnomAD3 genomes

AF:

0.782

AC:

118885

AN:

151998

Hom.:

47043

Cov.:

show subpopulations

Gnomad AFR

AF:

0.889

Gnomad AMI

AF:

0.806

Gnomad AMR

AF:

0.747

Gnomad ASJ

AF:

0.688

Gnomad EAS

AF:

0.921

Gnomad SAS

AF:

0.817

Gnomad FIN

AF:

0.812

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.713

Gnomad OTH

AF:

0.751

GnomAD4 exome

AF:

0.682

AC:

424

AN:

622

Hom.:

150

AF XY:

0.688

AC XY:

234

AN XY:

340

show subpopulations

Gnomad4 AFR exome

AF:

0.714

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.871

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.839

Gnomad4 NFE exome

AF:

0.643

Gnomad4 OTH exome

AF:

0.550

GnomAD4 genome

AF:

0.782

AC:

118987

AN:

152116

Hom.:

47089

Cov.:

AF XY:

0.786

AC XY:

58444

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.889

Gnomad4 AMR

AF:

0.748

Gnomad4 ASJ

AF:

0.688

Gnomad4 EAS

AF:

0.921

Gnomad4 SAS

AF:

0.817

Gnomad4 FIN

AF:

0.812

Gnomad4 NFE

AF:

0.713

Gnomad4 OTH

AF:

0.750

Alfa

AF:

0.738

Hom.:

4959

Bravo

AF:

0.782

Asia WGS

AF:

0.859

AC:

2988

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.14

DANN

Benign

0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over