rs2472533

Positions:

• chr10-1045623-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IDI1	NM_004508.4	c.141-1452G>A		intron_variant		ENST00000381344.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDI1	ENST00000381344.8	c.141-1452G>A		intron_variant		1	NM_004508.4

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

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.385

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2472533; hg19: chr10-1091563;