dbSNP rs1024131295: IDI1:p.Ala8Gly (chr10-1048981-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004508.4(IDI1):c.23C>G(p.Ala8Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000294 in 1,529,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

IDI1
NM_004508.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.686

Publications

0 publications found

Variant links:

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]

IDI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047066033).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004508.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IDI1	NM_004508.4	MANE Select	c.23C>G	p.Ala8Gly	missense	Exon 1 of 5	NP_004499.2
IDI1	NM_001317955.2		c.-28-4810C>G		intron	N/A	NP_001304884.1	A0A8Q3WKR8
IDI1	NR_134301.1		n.386C>G		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IDI1	ENST00000381344.8	TSL:1 MANE Select	c.23C>G	p.Ala8Gly	missense	Exon 1 of 5	ENSP00000370748.3	Q13907-2
IDI1	ENST00000491735.1	TSL:1	n.123C>G		non_coding_transcript_exon	Exon 1 of 4
IDI1	ENST00000695775.1		c.-146C>G		upstream_gene	N/A	ENSP00000512165.1	A0A8Q3WKR8

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000313

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000728

AC:

AN:

123638

AF XY:

0.0000730

show subpopulations

Gnomad AFR exome

AF:

0.000231

Gnomad AMR exome

AF:

0.0000435

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000124

Gnomad NFE exome

AF:

0.000126

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000196

AC:

AN:

1377546

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

680216

show subpopulations

African (AFR)

AF:

0.000136

AC:

AN:

29446

American (AMR)

AF:

0.0000290

AC:

AN:

34466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23872

East Asian (EAS)

AF:

0.00

AC:

AN:

34736

South Asian (SAS)

AF:

0.00

AC:

AN:

78046

European-Finnish (FIN)

AF:

0.0000259

AC:

AN:

38550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5320

European-Non Finnish (NFE)

AF:

0.0000195

AC:

AN:

1075756

Other (OTH)

AF:

0.00

AC:

AN:

57354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000118

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41590

American (AMR)

AF:

0.0000654

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000121

Hom.:

Bravo

AF:

0.000106

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.5

(source)

DANN

Benign

0.91

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.32

M_CAP

Benign

0.0086

MetaRNN

Benign

0.047

MetaSVM

Benign

-1.0

PhyloP100

-0.69

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.070

REVEL

Benign

0.0090

Sift

Benign

0.12

Sift4G

Benign

0.21

Polyphen

0.0

Vest4

0.15

MutPred

0.33

Loss of helix (P = 0.0237)

MVP

0.20

MPC

0.58

ClinPred

0.035

GERP RS

-0.23

PromoterAI

0.015

Neutral

(source)

gMVP

0.23

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over