10-92479610-AGTGTGTGTGTGT-AGTGTGTGTGTGTGT

Position:

• chr10-92479610-AGTGTGTGTGTGT-AGTGTGTGTGTGTGT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_004969.4(IDE):​c.1740-190_1740-189insAC 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
IDE	NM_004969.4	c.1740-190_1740-189insAC		intron_variant		ENST00000265986.11	NP_004960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IDE	ENST00000265986.11	c.1740-190_1740-189insAC		intron_variant		1	NM_004969.4	ENSP00000265986	P1

Frequencies

GnomAD3 genomes AF: 0.0721 AC: 10827 AN: 150074 Hom.: 1080 Cov.: 0

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.: 48 Cov.: 0 AF XY: 0.0238 AC XY: 3909 AN XY: 163978

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.0297

Gnomad4 ASJ exome AF: 0.0225

Gnomad4 EAS exome AF: 0.0306

Gnomad4 SAS exome AF: 0.0195

Gnomad4 FIN exome AF: 0.0100

Gnomad4 NFE exome AF: 0.0181

Gnomad4 OTH exome AF: 0.0314

GnomAD4 genome AF: 0.0722 AC: 10843 AN: 150172 Hom.: 1083 Cov.: 0 AF XY: 0.0691 AC XY: 5064 AN XY: 73292

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.0342

Gnomad4 ASJ AF: 0.0185

Gnomad4 EAS AF: 0.00991

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.00375

Gnomad4 NFE AF: 0.0118

Gnomad4 OTH AF: 0.0577

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3831274; hg19: chr10-94239367;