dbSNP rs17875327: IDE:c.662-10T>C (chr10-92515052-A-G) – 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.662-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 1,568,604 control chromosomes in the GnomAD database, including 7,869 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 0.072 ( 566 hom., cov: 32)

Exomes 𝑓: 0.094 ( 7303 hom. )

Consequence

IDE
NM_004969.4 intron

Scores

Splicing: ADA: 0.3518

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDE	NM_004969.4 link	c.662-10T>C		intron_variant	Intron 4 of 24	ENST00000265986.11	NP_004960.2	P14735-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDE	ENST00000265986.11 link	c.662-10T>C		intron_variant	Intron 4 of 24	1	NM_004969.4	ENSP00000265986.6		P14735-1

Frequencies

GnomAD3 genomes

AF:

0.0719

AC:

10928

AN:

152056

Hom.:

566

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0158

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.0518

Gnomad ASJ

AF:

0.0691

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0318

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.0607

GnomAD3 exomes

AF:

0.0805

AC:

18109

AN:

224962

Hom.:

1020

AF XY:

0.0815

AC XY:

9921

AN XY:

121736

show subpopulations

Gnomad AFR exome

AF:

0.0156

Gnomad AMR exome

AF:

0.0380

Gnomad ASJ exome

AF:

0.0788

Gnomad EAS exome

AF:

0.000295

Gnomad SAS exome

AF:

0.0308

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.0829

GnomAD4 exome

AF:

0.0938

AC:

132923

AN:

1416428

Hom.:

7303

Cov.:

AF XY:

0.0926

AC XY:

65002

AN XY:

702312

show subpopulations

Gnomad4 AFR exome

AF:

0.0128

Gnomad4 AMR exome

AF:

0.0389

Gnomad4 ASJ exome

AF:

0.0735

Gnomad4 EAS exome

AF:

0.000153

Gnomad4 SAS exome

AF:

0.0303

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.0774

GnomAD4 genome

AF:

0.0718

AC:

10920

AN:

152176

Hom.:

566

Cov.:

AF XY:

0.0721

AC XY:

5363

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0157

Gnomad4 AMR

AF:

0.0516

Gnomad4 ASJ

AF:

0.0691

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0312

Gnomad4 FIN

AF:

0.166

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.0601

Alfa

AF:

0.0788

Hom.:

195

Bravo

AF:

0.0606

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.35

dbscSNV1_RF

Benign

0.40

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

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