8-39908329-C-T

Variant names:

• chr8-39908329-C-T
• rs9657182
• ENST00000522495.5:c.-182-4672C>T

Variant summary

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

The ENST00000522495.5(IDO1):​c.-182-4672C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,564 control chromosomes in the GnomAD database, including 28,772 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 0.60 (28772 hom., cov: 30)
• Consequence: IDO1 ENST00000522495.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 30 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=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDO1	ENST00000522495.5	c.-182-4672C>T		intron_variant	Intron 1 of 11	5		ENSP00000430505.1
IDO1	ENST00000519154.5	c.-520-5074C>T		intron_variant	Intron 1 of 6	5		ENSP00000428716.1
IDO1	ENST00000518804.5	c.-204-850C>T		intron_variant	Intron 1 of 4	4		ENSP00000429297.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91364 AN: 151456 Hom.: 28734 Cov.: 30

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.619

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.603 AC: 91447 AN: 151564 Hom.: 28772 Cov.: 30 AF XY: 0.593 AC XY: 43873 AN XY: 74012

African (AFR) AF: 0.775 AC: 32083 AN: 41394

American (AMR) AF: 0.507 AC: 7694 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2004 AN: 3470

East Asian (EAS) AF: 0.507 AC: 2609 AN: 5150

South Asian (SAS) AF: 0.333 AC: 1598 AN: 4804

European-Finnish (FIN) AF: 0.529 AC: 5511 AN: 10408

Middle Eastern (MID) AF: 0.625 AC: 180 AN: 288

European-Non Finnish (NFE) AF: 0.560 AC: 37987 AN: 67870

Other (OTH) AF: 0.598 AC: 1258 AN: 2102

Alfa AF: 0.584 Hom.: 42708

Bravo AF: 0.615

Asia WGS AF: 0.423 AC: 1474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.4
DANN	Benign	0.50
PhyloP100		-2.2
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: rs9657182; hg19: chr8-39765848;