Genetic Variant NM_004969.4:c.1740-191_1740-190dupAC (chr10-92479610-A-AGT) – 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_1740-190dupAC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.072 ( 1083 hom., cov: 0)

Exomes 𝑓: 0.025 ( 48 hom. )

Consequence

IDE
NM_004969.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.809

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 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_1740-190dupAC		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_1740-190dupAC		intron_variant	Intron 14 of 24	1	NM_004969.4	ENSP00000265986.6		P14735-1

Frequencies

GnomAD3 genomes

AF:

0.0721

AC:

10827

AN:

150074

Hom.:

1080

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.00773

Gnomad AMR

AF:

0.0343

Gnomad ASJ

AF:

0.0185

Gnomad EAS

AF:

0.00989

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.00375

Gnomad MID

AF:

0.0353

Gnomad NFE

AF:

0.0118

Gnomad OTH

AF:

0.0583

GnomAD4 exome

AF:

0.0254

AC:

7961

AN:

313540

Hom.:

Cov.:

AF XY:

0.0238

AC XY:

3909

AN XY:

163978

show subpopulations

African (AFR)

AF:

0.190

AC:

1850

AN:

9730

American (AMR)

AF:

0.0297

AC:

416

AN:

13992

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

225

AN:

10004

East Asian (EAS)

AF:

0.0306

AC:

683

AN:

22346

South Asian (SAS)

AF:

0.0195

AC:

512

AN:

26202

European-Finnish (FIN)

AF:

0.0100

AC:

214

AN:

21326

Middle Eastern (MID)

AF:

0.0324

AC:

AN:

1388

European-Non Finnish (NFE)

AF:

0.0181

AC:

3428

AN:

189824

Other (OTH)

AF:

0.0314

AC:

588

AN:

18728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

297

595

892

1190

1487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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:

0.0722

AC:

10843

AN:

150172

Hom.:

1083

Cov.:

AF XY:

0.0691

AC XY:

5064

AN XY:

73292

show subpopulations

African (AFR)

AF:

0.223

AC:

9171

AN:

41034

American (AMR)

AF:

0.0342

AC:

515

AN:

15058

Ashkenazi Jewish (ASJ)

AF:

0.0185

AC:

AN:

3410

East Asian (EAS)

AF:

0.00991

AC:

AN:

5146

South Asian (SAS)

AF:

0.0147

AC:

AN:

4756

European-Finnish (FIN)

AF:

0.00375

AC:

AN:

10126

Middle Eastern (MID)

AF:

0.0345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0118

AC:

798

AN:

67368

Other (OTH)

AF:

0.0577

AC:

120

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

420

840

1261

1681

2101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.00625

Hom.:

211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.81

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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