10-92453329-TTA-TTATA

Variant names:

• chr10-92453329-T-TTA
• rs5786997
• NM_004969.4:c.*1113_*1114dupTA

Variant summary

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

The NM_004969.4(IDE):​c.*1113_*1114dupTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.068 in 152,256 control chromosomes in the GnomAD database, including 532 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.068 (532 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IDE NM_004969.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• Publications: 4 publications found

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]

ACMG classification

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

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0979 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004969.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDE	NM_004969.4	MANE Select	c.*1113_*1114dupTA		3_prime_UTR	Exon 25 of 25	NP_004960.2
	IDE	NR_136399.2		n.4371_4372dupTA		non_coding_transcript_exon	Exon 26 of 26
	IDE	NM_001322793.2		c.*1113_*1114dupTA		3_prime_UTR	Exon 25 of 25	NP_001309722.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDE	ENST00000265986.11	TSL:1 MANE Select	c.*1113_*1114dupTA		3_prime_UTR	Exon 25 of 25	ENSP00000265986.6
	IDE	ENST00000676626.1		n.4918_4919dupTA		non_coding_transcript_exon	Exon 25 of 25
	IDE	ENST00000676816.1		n.*1408_*1409dupTA		non_coding_transcript_exon	Exon 26 of 26	ENSP00000504709.1

Frequencies

GnomAD3 genomes AF: 0.0681 AC: 10361 AN: 152138 Hom.: 532 Cov.: 32

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.0525

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0929

Gnomad FIN AF: 0.0792

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0999

Gnomad OTH AF: 0.0679

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0680 AC: 10356 AN: 152256 Hom.: 532 Cov.: 32 AF XY: 0.0670 AC XY: 4989 AN XY: 74432

African (AFR) AF: 0.0171 AC: 711 AN: 41572

American (AMR) AF: 0.0525 AC: 803 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0704 AC: 244 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5192

South Asian (SAS) AF: 0.0922 AC: 445 AN: 4828

European-Finnish (FIN) AF: 0.0792 AC: 839 AN: 10592

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0999 AC: 6792 AN: 68000

Other (OTH) AF: 0.0667 AC: 141 AN: 2114

Alfa AF: 0.0154 Hom.: 6

Bravo AF: 0.0645

Asia WGS AF: 0.0320 AC: 110 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs5786997; hg19: chr10-94213086;