NM_004508.4:c.141-1084C>T

Variant names:

• chr10-1045255-G-A
• rs7075141
• NM_004508.4:c.141-1084C>T

Variant summary

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

The NM_004508.4(IDI1):​c.141-1084C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,230 control chromosomes in the GnomAD database, including 33,802 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 0.66 (33802 hom., cov: 35)
• Consequence: IDI1 NM_004508.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDI1	NM_004508.4	c.141-1084C>T		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.141-1084C>T		intron_variant	Intron 1 of 4	1	NM_004508.4	ENSP00000370748.3

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100252 AN: 152112 Hom.: 33752 Cov.: 35

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.659 AC: 100354 AN: 152230 Hom.: 33802 Cov.: 35 AF XY: 0.670 AC XY: 49850 AN XY: 74436

African (AFR) AF: 0.532 AC: 22103 AN: 41510

American (AMR) AF: 0.715 AC: 10939 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2204 AN: 3470

East Asian (EAS) AF: 0.826 AC: 4287 AN: 5192

South Asian (SAS) AF: 0.757 AC: 3659 AN: 4832

European-Finnish (FIN) AF: 0.806 AC: 8545 AN: 10600

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46365 AN: 68006

Other (OTH) AF: 0.650 AC: 1370 AN: 2108

Alfa AF: 0.685 Hom.: 31487

Bravo AF: 0.645

Asia WGS AF: 0.764 AC: 2655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.54
DANN	Benign	0.59
PhyloP100		-1.4
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: rs7075141; hg19: chr10-1091195;