8-39912430-G-C

Variant names:

• chr8-39912430-G-C
• rs10089084
• ENST00000522495.5:c.-182-571G>C

Variant summary

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

The ENST00000522495.5(IDO1):​c.-182-571G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,788 control chromosomes in the GnomAD database, including 7,291 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 0.30 (7291 hom., cov: 33)
• Consequence: IDO1 ENST00000522495.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• Publications: 11 publications found

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]

ENSG00000253939 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000522495.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDO1	ENST00000522495.5	TSL:5	c.-182-571G>C		intron	N/A	ENSP00000430505.1
	IDO1	ENST00000519154.5	TSL:5	c.-520-973G>C		intron	N/A	ENSP00000428716.1
	IDO1	ENST00000518804.5	TSL:4	c.-34-1459G>C		intron	N/A	ENSP00000429297.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46043 AN: 151670 Hom.: 7286 Cov.: 33

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.303 AC: 46054 AN: 151788 Hom.: 7291 Cov.: 33 AF XY: 0.298 AC XY: 22089 AN XY: 74192

African (AFR) AF: 0.268 AC: 11076 AN: 41402

American (AMR) AF: 0.233 AC: 3559 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1350 AN: 3466

East Asian (EAS) AF: 0.243 AC: 1252 AN: 5152

South Asian (SAS) AF: 0.192 AC: 926 AN: 4814

European-Finnish (FIN) AF: 0.274 AC: 2886 AN: 10540

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23866 AN: 67848

Other (OTH) AF: 0.318 AC: 669 AN: 2102

Alfa AF: 0.328 Hom.: 1052

Bravo AF: 0.301

Asia WGS AF: 0.210 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.74
DANN	Benign	0.67
PhyloP100		-0.28
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: rs10089084; hg19: chr8-39769949;