rs3831274

chr10-92479610-AGTGTGTGTGTGT-Achr10-92479610-AGTGTGTGTGTGT-AGTchr10-92479610-AGTGTGTGTGTGT-AGTGTchr10-92479610-AGTGTGTGTGTGT-AGTGTGTchr10-92479610-AGTGTGTGTGTGT-AGTGTGTGTchr10-92479610-AGTGTGTGTGTGT-AGTGTGTGTGTchr10-92479610-AGTGTGTGTGTGT-AGTGTGTGTGTGTGTchr10-92479610-AGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTchr10-92479610-AGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTchr10-92479610-AGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004969.4(IDE):c.1740-201_1740-190del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 320,100 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.969

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IDE	NM_004969.4	c.1740-201_1740-190del		intron_variant		ENST00000265986.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDE	ENST00000265986.11	c.1740-201_1740-190del		intron_variant		1	NM_004969.4	P1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000312 AC: 1 AN: 320100 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 167342

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000515

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

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;