Genetic Variant NM_004969.4:c.1060+151C>T (chr10-92508577-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004969.4(IDE):c.1060+151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 507,410 control chromosomes in the GnomAD database, including 8,381 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 0.20 ( 3163 hom., cov: 29)

Exomes 𝑓: 0.15 ( 5218 hom. )

Consequence

IDE
NM_004969.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.575

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDE	NM_004969.4 link	c.1060+151C>T		intron_variant	Intron 7 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.1060+151C>T		intron_variant	Intron 7 of 24	1	NM_004969.4	ENSP00000265986.6		P14735-1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

28291

AN:

144474

Hom.:

3159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.0702

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.0700

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.164

GnomAD4 exome

AF:

0.149

AC:

54058

AN:

362918

Hom.:

5218

AF XY:

0.149

AC XY:

27963

AN XY:

187858

show subpopulations

African (AFR)

AF:

0.254

AC:

2595

AN:

10220

American (AMR)

AF:

0.314

AC:

4170

AN:

13268

Ashkenazi Jewish (ASJ)

AF:

0.0718

AC:

755

AN:

10518

East Asian (EAS)

AF:

0.262

AC:

6860

AN:

26226

South Asian (SAS)

AF:

0.178

AC:

3600

AN:

20186

European-Finnish (FIN)

AF:

0.139

AC:

3485

AN:

25020

Middle Eastern (MID)

AF:

0.0694

AC:

143

AN:

2062

European-Non Finnish (NFE)

AF:

0.126

AC:

29477

AN:

234398

Other (OTH)

AF:

0.141

AC:

2973

AN:

21020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1858

3717

5575

7434

9292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.196

AC:

28316

AN:

144492

Hom.:

3163

Cov.:

AF XY:

0.197

AC XY:

13763

AN XY:

69902

show subpopulations

African (AFR)

AF:

0.268

AC:

10644

AN:

39732

American (AMR)

AF:

0.277

AC:

4028

AN:

14540

Ashkenazi Jewish (ASJ)

AF:

0.0702

AC:

239

AN:

3404

East Asian (EAS)

AF:

0.215

AC:

1063

AN:

4940

South Asian (SAS)

AF:

0.200

AC:

922

AN:

4600

European-Finnish (FIN)

AF:

0.141

AC:

1110

AN:

7876

Middle Eastern (MID)

AF:

0.0725

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.148

AC:

9820

AN:

66214

Other (OTH)

AF:

0.166

AC:

333

AN:

2008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1054

2109

3163

4218

5272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.163

Hom.:

517

Bravo

AF:

0.207

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.16

(source)

DANN

Benign

0.56

PhyloP100

-0.57

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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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