rs7910605

Variant names:

• chr10-92480036-A-G
• rs7910605
• NM_004969.4:c.1740-615T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004969.4(IDE):​c.1740-615T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,244 control chromosomes in the GnomAD database, including 2,528 homozygotes. 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 0.17 (2528 hom., cov: 33)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDE	NM_004969.4	MANE Select	c.1740-615T>C		intron	N/A	NP_004960.2	P14735-1
	IDE	NM_001322793.2		c.1740-1247T>C		intron	N/A	NP_001309722.1	A0A3B3ISG5
	IDE	NM_001322794.2		c.1623-615T>C		intron	N/A	NP_001309723.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDE	ENST00000265986.11	TSL:1 MANE Select	c.1740-615T>C		intron	N/A	ENSP00000265986.6	P14735-1
	IDE	ENST00000478361.6	TSL:1	n.*2074-615T>C		intron	N/A	ENSP00000473506.1	R4GN65
	IDE	ENST00000971392.1		c.1740-615T>C		intron	N/A	ENSP00000641451.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25960 AN: 152124 Hom.: 2524 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.0625

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.171 AC: 26008 AN: 152244 Hom.: 2528 Cov.: 33 AF XY: 0.172 AC XY: 12824 AN XY: 74444

African (AFR) AF: 0.245 AC: 10187 AN: 41518

American (AMR) AF: 0.223 AC: 3410 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0625 AC: 217 AN: 3470

East Asian (EAS) AF: 0.181 AC: 938 AN: 5182

South Asian (SAS) AF: 0.188 AC: 910 AN: 4828

European-Finnish (FIN) AF: 0.133 AC: 1413 AN: 10616

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8583 AN: 68012

Other (OTH) AF: 0.141 AC: 299 AN: 2114

Alfa AF: 0.143 Hom.: 5101

Bravo AF: 0.180

Asia WGS AF: 0.174 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.91
PhyloP100		1.5
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: rs7910605; hg19: chr10-94239793;