Variant rs4646954 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_004969.4(IDE):c.-51C>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.107 in 1,418,436 control chromosomes in the GnomAD database, including 10,783 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 0.16 ( 2824 hom., cov: 33)

Exomes 𝑓: 0.10 ( 7959 hom. )

Consequence

IDE
NM_004969.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.70

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:

KIF11 (HGNC:6388): (kinesin family member 11) This gene encodes a motor protein that belongs to the kinesin-like protein family. Members of this protein family are known to be involved in various kinds of spindle dynamics. The function of this gene product includes chromosome positioning, centrosome separation and establishing a bipolar spindle during cell mitosis. [provided by RefSeq, Jul 2008]

KIF11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IDE	NM_004969.4 linkuse as main transcript	c.-51C>T		5_prime_UTR_variant	1/25	ENST00000265986.11	NP_004960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IDE	ENST00000265986.11 linkuse as main transcript	c.-51C>T		5_prime_UTR_variant	1/25	1	NM_004969.4	ENSP00000265986	P1	P14735-1

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24406

AN:

152126

Hom.:

2812

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.0545

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.0542

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0879

Gnomad OTH

AF:

0.142

GnomAD3 exomes

AF:

0.131

AC:

12453

AN:

95136

Hom.:

1160

AF XY:

0.127

AC XY:

6712

AN XY:

52986

show subpopulations

Gnomad AFR exome

AF:

0.338

Gnomad AMR exome

AF:

0.240

Gnomad ASJ exome

AF:

0.0503

Gnomad EAS exome

AF:

0.113

Gnomad SAS exome

AF:

0.164

Gnomad FIN exome

AF:

0.0623

Gnomad NFE exome

AF:

0.0846

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.100

AC:

127246

AN:

1266192

Hom.:

7959

Cov.:

AF XY:

0.102

AC XY:

64109

AN XY:

628302

show subpopulations

Gnomad4 AFR exome

AF:

0.327

Gnomad4 AMR exome

AF:

0.220

Gnomad4 ASJ exome

AF:

0.0514

Gnomad4 EAS exome

AF:

0.177

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.0658

Gnomad4 NFE exome

AF:

0.0864

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.161

AC:

24459

AN:

152244

Hom.:

2824

Cov.:

AF XY:

0.159

AC XY:

11835

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.318

Gnomad4 AMR

AF:

0.178

Gnomad4 ASJ

AF:

0.0545

Gnomad4 EAS

AF:

0.127

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.0542

Gnomad4 NFE

AF:

0.0879

Gnomad4 OTH

AF:

0.144

Alfa

AF:

0.0902

Hom.:

751

Bravo

AF:

0.176

Asia WGS

AF:

0.148

AC:

517

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.96

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

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