10-92557873-T-G

Variant names:

• chr10-92557873-T-G
• rs12412249
• NM_004969.4:c.98+16049A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004969.4(IDE):​c.98+16049A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.48 (4758 hom., cov: 10)
  • Failed GnomAD Quality Control
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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.98+16049A>C		intron	N/A	NP_004960.2
	IDE	NM_001322793.2		c.98+16049A>C		intron	N/A	NP_001309722.1
	IDE	NM_001322794.2		c.98+16049A>C		intron	N/A	NP_001309723.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDE	ENST00000265986.11	TSL:1 MANE Select	c.98+16049A>C		intron	N/A	ENSP00000265986.6
	IDE	ENST00000478361.6	TSL:1	n.*223+921A>C		intron	N/A	ENSP00000473506.1
	IDE	ENST00000650060.2		c.98+16049A>C		intron	N/A	ENSP00000497272.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 34311 AN: 70756 Hom.: 4756 Cov.: 10

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.447

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.477

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.485 AC: 34308 AN: 70744 Hom.: 4758 Cov.: 10 AF XY: 0.485 AC XY: 16267 AN XY: 33546

African (AFR) AF: 0.465 AC: 6841 AN: 14720

American (AMR) AF: 0.505 AC: 3676 AN: 7286

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 882 AN: 1826

East Asian (EAS) AF: 0.424 AC: 730 AN: 1722

South Asian (SAS) AF: 0.481 AC: 1147 AN: 2386

European-Finnish (FIN) AF: 0.513 AC: 1774 AN: 3456

Middle Eastern (MID) AF: 0.450 AC: 63 AN: 140

European-Non Finnish (NFE) AF: 0.490 AC: 18626 AN: 37986

Other (OTH) AF: 0.477 AC: 449 AN: 942

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.261

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.36
PhyloP100		0.055
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12412249; hg19: chr10-94317630;