rs35059413

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002164.6(IDO1):c.10G>A(p.Ala4Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,569,164 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0099 ( 24 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 15 hom. )

Consequence

IDO1
NM_002164.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.215

Publications

7 publications found

Variant links:

Genes affected

IDO1 (HGNC:6059): (indoleamine 2,3-dioxygenase 1) This gene encodes indoleamine 2,3-dioxygenase (IDO) - a heme enzyme that catalyzes the first and rate-limiting step in tryptophan catabolism to N-formyl-kynurenine. This enzyme acts on multiple tryptophan substrates including D-tryptophan, L-tryptophan, 5-hydroxy-tryptophan, tryptamine, and serotonin. This enzyme is thought to play a role in a variety of pathophysiological processes such as antimicrobial and antitumor defense, neuropathology, immunoregulation, and antioxidant activity. Through its expression in dendritic cells, monocytes, and macrophages this enzyme modulates T-cell behavior by its peri-cellular catabolization of the essential amino acid tryptophan.[provided by RefSeq, Feb 2011]

IDO1 links:

ENSG00000253939 (HGNC:):

ENSG00000253939 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028638542).

BP6

Variant 8-39913932-G-A is Benign according to our data. Variant chr8-39913932-G-A is described in ClinVar as Benign. ClinVar VariationId is 786116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00994 (1514/152288) while in subpopulation AFR AF = 0.0337 (1400/41550). AF 95% confidence interval is 0.0322. There are 24 homozygotes in GnomAd4. There are 721 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDO1	NM_002164.6 link	c.10G>A	p.Ala4Thr	missense_variant	Exon 1 of 10	ENST00000518237.6	NP_002155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDO1	ENST00000518237.6 link	c.10G>A	p.Ala4Thr	missense_variant	Exon 1 of 10	1	NM_002164.6	ENSP00000430950.1

Frequencies

GnomAD3 genomes

AF:

0.00991

AC:

1508

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0336

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00589

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:

0.0000735

Gnomad OTH

AF:

0.00910

GnomAD2 exomes

AF:

0.00217

AC:

400

AN:

184434

AF XY:

0.00158

show subpopulations

Gnomad AFR exome

AF:

0.0324

Gnomad AMR exome

AF:

0.00184

Gnomad ASJ exome

AF:

0.000112

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000255

Gnomad OTH exome

AF:

0.00161

GnomAD4 exome

AF:

0.00106

AC:

1507

AN:

1416876

Hom.:

Cov.:

AF XY:

0.000915

AC XY:

641

AN XY:

700414

show subpopulations

African (AFR)

AF:

0.0377

AC:

1219

AN:

32322

American (AMR)

AF:

0.00238

AC:

AN:

37452

Ashkenazi Jewish (ASJ)

AF:

0.0000394

AC:

AN:

25364

East Asian (EAS)

AF:

0.00

AC:

AN:

37412

South Asian (SAS)

AF:

0.000187

AC:

AN:

80106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50742

Middle Eastern (MID)

AF:

0.00140

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.0000165

AC:

AN:

1088824

Other (OTH)

AF:

0.00266

AC:

157

AN:

58942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

130

194

259

324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.00994

AC:

1514

AN:

152288

Hom.:

Cov.:

AF XY:

0.00968

AC XY:

721

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0337

AC:

1400

AN:

41550

American (AMR)

AF:

0.00588

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68018

Other (OTH)

AF:

0.00900

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

151

226

302

377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00363

Hom.:

Bravo

AF:

0.0117

ESP6500AA

AF:

0.0285

AC:

111

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.00220

AC:

262

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

2.0

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0064

T;.;T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.56

T;T;.;T;T

MetaRNN

Benign

0.0029

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;.;N;.;N

PhyloP100

-0.21

PrimateAI

Benign

0.25

PROVEAN

Benign

0.28

N;N;N;N;N

REVEL

Benign

0.016

Sift

Benign

0.94

T;T;T;T;T

Sift4G

Benign

0.32

T;T;T;T;T

Polyphen

0.047

.;.;B;.;B

Vest4

0.015, 0.0050

MVP

0.13

MPC

0.039

ClinPred

0.00093

GERP RS

-0.40

PromoterAI

-0.067

Neutral

(source)

Varity_R

0.030

gMVP

0.34

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over