rs1832196

Variant names:

• chr10-92508577-G-A
• rs1832196
• NM_004969.4:c.1060+151C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-92508577-G-A
• chr10-92508577-G-T

Variant summary

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

The NM_004969.4(IDE):​c.1060+151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 507,410 control chromosomes in the GnomAD database, including 8,381 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 0.20 (3163 hom., cov: 29)
  • Exomes 𝑓: 0.15 (5218 hom.)
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 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.1060+151C>T		intron	N/A	NP_004960.2	P14735-1
	IDE	NM_001322793.2		c.1060+151C>T		intron	N/A	NP_001309722.1	A0A3B3ISG5
	IDE	NM_001322794.2		c.943+151C>T		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.1060+151C>T		intron	N/A	ENSP00000265986.6	P14735-1
	IDE	ENST00000478361.6	TSL:1	n.*1270+151C>T		intron	N/A	ENSP00000473506.1	R4GN65
	IDE	ENST00000971392.1		c.1060+151C>T		intron	N/A	ENSP00000641451.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 28291 AN: 144474 Hom.: 3159 Cov.: 29

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.0702

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0700

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.149 AC: 54058 AN: 362918 Hom.: 5218 AF XY: 0.149 AC XY: 27963 AN XY: 187858

African (AFR) AF: 0.254 AC: 2595 AN: 10220

American (AMR) AF: 0.314 AC: 4170 AN: 13268

Ashkenazi Jewish (ASJ) AF: 0.0718 AC: 755 AN: 10518

East Asian (EAS) AF: 0.262 AC: 6860 AN: 26226

South Asian (SAS) AF: 0.178 AC: 3600 AN: 20186

European-Finnish (FIN) AF: 0.139 AC: 3485 AN: 25020

Middle Eastern (MID) AF: 0.0694 AC: 143 AN: 2062

European-Non Finnish (NFE) AF: 0.126 AC: 29477 AN: 234398

Other (OTH) AF: 0.141 AC: 2973 AN: 21020

GnomAD4 genome AF: 0.196 AC: 28316 AN: 144492 Hom.: 3163 Cov.: 29 AF XY: 0.197 AC XY: 13763 AN XY: 69902

African (AFR) AF: 0.268 AC: 10644 AN: 39732

American (AMR) AF: 0.277 AC: 4028 AN: 14540

Ashkenazi Jewish (ASJ) AF: 0.0702 AC: 239 AN: 3404

East Asian (EAS) AF: 0.215 AC: 1063 AN: 4940

South Asian (SAS) AF: 0.200 AC: 922 AN: 4600

European-Finnish (FIN) AF: 0.141 AC: 1110 AN: 7876

Middle Eastern (MID) AF: 0.0725 AC: 20 AN: 276

European-Non Finnish (NFE) AF: 0.148 AC: 9820 AN: 66214

Other (OTH) AF: 0.166 AC: 333 AN: 2008

Alfa AF: 0.163 Hom.: 517

Bravo AF: 0.207

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.16
DANN	Benign	0.56
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1832196; hg19: chr10-94268334;