NM_004969.4:c.98+16049A>T

Variant names:

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

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>T 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 0.00043 (0 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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDE	NM_004969.4	c.98+16049A>T		intron_variant	Intron 1 of 24	ENST00000265986.11	NP_004960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDE	ENST00000265986.11	c.98+16049A>T		intron_variant	Intron 1 of 24	1	NM_004969.4	ENSP00000265986.6

Frequencies

GnomAD3 genomes AF: 0.000435 AC: 31 AN: 71282 Hom.: 0 Cov.: 10

Gnomad AFR AF: 0.000337

Gnomad AMI AF: 0.00357

Gnomad AMR AF: 0.000409

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00286

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00143

Gnomad MID AF: 0.00649

Gnomad NFE AF: 0.000261

Gnomad OTH AF: 0.00

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: AS_VQSR AF: 0.000435 AC: 31 AN: 71270 Hom.: 0 Cov.: 10 AF XY: 0.000444 AC XY: 15 AN XY: 33818

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000337 AC: 5 AN: 14840

American (AMR) AF: 0.000409 AC: 3 AN: 7336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1834

East Asian (EAS) AF: 0.00287 AC: 5 AN: 1742

South Asian (SAS) AF: 0.000416 AC: 1 AN: 2406

European-Finnish (FIN) AF: 0.00143 AC: 5 AN: 3506

Middle Eastern (MID) AF: 0.00704 AC: 1 AN: 142

European-Non Finnish (NFE) AF: 0.000262 AC: 10 AN: 38238

Other (OTH) AF: 0.00 AC: 0 AN: 946

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.40
PhyloP100		0.055

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;