Genetic Variant IDE:c.1740-191_1740-190delAC (chr10-92479610-AGT-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004969.4(IDE):c.1740-191_1740-190delAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 454,762 control chromosomes in the GnomAD database, including 16,677 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 7656 hom., cov: 0)

Exomes 𝑓: 0.33 ( 9021 hom. )

Consequence

IDE
NM_004969.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.481

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDE	NM_004969.4 link	c.1740-191_1740-190delAC		intron_variant	Intron 14 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.1740-191_1740-190delAC		intron_variant	Intron 14 of 24	1	NM_004969.4	ENSP00000265986.6		P14735-1

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

43539

AN:

149960

Hom.:

7661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0953

Gnomad AMI

AF:

0.496

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.660

Gnomad SAS

AF:

0.480

Gnomad FIN

AF:

0.397

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.350

Gnomad OTH

AF:

0.311

GnomAD4 exome

AF:

0.328

AC:

99813

AN:

304706

Hom.:

9021

AF XY:

0.330

AC XY:

52547

AN XY:

159248

show subpopulations

African (AFR)

AF:

0.120

AC:

1123

AN:

9344

American (AMR)

AF:

0.264

AC:

3582

AN:

13554

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

3234

AN:

9638

East Asian (EAS)

AF:

0.519

AC:

11453

AN:

22080

South Asian (SAS)

AF:

0.344

AC:

8887

AN:

25828

European-Finnish (FIN)

AF:

0.347

AC:

7207

AN:

20776

Middle Eastern (MID)

AF:

0.315

AC:

426

AN:

1352

European-Non Finnish (NFE)

AF:

0.316

AC:

58028

AN:

183902

Other (OTH)

AF:

0.322

AC:

5873

AN:

18232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

3198

6396

9595

12793

15991

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

410

820

1230

1640

2050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.290

AC:

43535

AN:

150056

Hom.:

7656

Cov.:

AF XY:

0.296

AC XY:

21697

AN XY:

73204

show subpopulations

African (AFR)

AF:

0.0951

AC:

3906

AN:

41052

American (AMR)

AF:

0.264

AC:

3971

AN:

15024

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1188

AN:

3406

East Asian (EAS)

AF:

0.660

AC:

3397

AN:

5144

South Asian (SAS)

AF:

0.481

AC:

2286

AN:

4752

European-Finnish (FIN)

AF:

0.397

AC:

4017

AN:

10112

Middle Eastern (MID)

AF:

0.316

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.350

AC:

23583

AN:

67298

Other (OTH)

AF:

0.312

AC:

647

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1422

2843

4265

5686

7108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.135

Hom.:

211

Bravo

AF:

0.277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.48

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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10-92479610-AGTGTGTGTGTGT-AGTGTGTGTGT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over