rs2472533

Variant names:

• chr10-1045623-C-T
• rs2472533
• NM_004508.4:c.141-1452G>A

Variant summary

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

The NM_004508.4(IDI1):​c.141-1452G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,062 control chromosomes in the GnomAD database, including 12,179 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 0.39 (12179 hom., cov: 34)
• Consequence: IDI1 NM_004508.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763
• Publications: 5 publications found

Genes affected

IDI1 (HGNC:5387): (isopentenyl-diphosphate delta isomerase 1) IDI1 encodes a peroxisomally-localized enzyme that catalyzes the interconversion of isopentenyl diphosphate (IPP) to its highly electrophilic isomer, dimethylallyl diphosphate (DMAPP), which are the substrates for the successive reaction that results in the synthesis of farnesyl diphosphate and, ultimately, cholesterol. It has been shown in peroxisomal deficiency diseases such as Zellweger syndrome and neonatal adrenoleukodystrophy that there is reduction in IPP isomerase activity. [provided by RefSeq, Jul 2008]

IDI2-AS1 (HGNC:30885): (IDI2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDI1	NM_004508.4	c.141-1452G>A		intron_variant	Intron 1 of 4	ENST00000381344.8	NP_004499.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDI1	ENST00000381344.8	c.141-1452G>A		intron_variant	Intron 1 of 4	1	NM_004508.4	ENSP00000370748.3

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59203 AN: 151942 Hom.: 12155 Cov.: 34

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.390 AC: 59241 AN: 152062 Hom.: 12179 Cov.: 34 AF XY: 0.398 AC XY: 29570 AN XY: 74304

African (AFR) AF: 0.255 AC: 10568 AN: 41488

American (AMR) AF: 0.422 AC: 6451 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1358 AN: 3472

East Asian (EAS) AF: 0.536 AC: 2771 AN: 5166

South Asian (SAS) AF: 0.528 AC: 2547 AN: 4820

European-Finnish (FIN) AF: 0.511 AC: 5387 AN: 10548

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28955 AN: 67962

Other (OTH) AF: 0.385 AC: 812 AN: 2108

Alfa AF: 0.415 Hom.: 1698

Bravo AF: 0.373

Asia WGS AF: 0.520 AC: 1809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.76
PhyloP100		-0.76
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: rs2472533; hg19: chr10-1091563;