8-39912074-C-A

Variant names:

• chr8-39912074-C-A
• rs3824259
• ENST00000522495.5:c.-182-927C>A

Variant summary

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

The ENST00000522495.5(IDO1):​c.-182-927C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 151,578 control chromosomes in the GnomAD database, including 28,159 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 0.59 (28159 hom., cov: 31)
• Consequence: IDO1 ENST00000522495.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 13 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 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.-182-927C>A		intron_variant	Intron 1 of 11	5		ENSP00000430505.1
IDO1	ENST00000519154.5	c.-520-1329C>A		intron_variant	Intron 1 of 6	5		ENSP00000428716.1
IDO1	ENST00000518804.5	c.-34-1815C>A		intron_variant	Intron 2 of 4	4		ENSP00000429297.1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 89836 AN: 151478 Hom.: 28111 Cov.: 31

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.593 AC: 89932 AN: 151578 Hom.: 28159 Cov.: 31 AF XY: 0.583 AC XY: 43121 AN XY: 73980

African (AFR) AF: 0.804 AC: 33301 AN: 41436

American (AMR) AF: 0.497 AC: 7563 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1946 AN: 3466

East Asian (EAS) AF: 0.502 AC: 2584 AN: 5152

South Asian (SAS) AF: 0.328 AC: 1570 AN: 4790

European-Finnish (FIN) AF: 0.488 AC: 5050 AN: 10338

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 35987 AN: 67886

Other (OTH) AF: 0.592 AC: 1241 AN: 2098

Alfa AF: 0.557 Hom.: 4133

Bravo AF: 0.609

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.31
PhyloP100		0.041
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: rs3824259; hg19: chr8-39769593;