chr8-39911856-A-G

Variant names:

• chr8-39911856-A-G
• rs3808606
• ENST00000522495.5:c.-182-1145A>G

Variant summary

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

The ENST00000522495.5(IDO1):​c.-182-1145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,032 control chromosomes in the GnomAD database, including 27,069 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 0.58 (27069 hom., cov: 32)
• Consequence: IDO1 ENST00000522495.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598
• Publications: 15 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDO1	ENST00000522495.5	TSL:5	c.-182-1145A>G		intron	N/A	ENSP00000430505.1
	IDO1	ENST00000519154.5	TSL:5	c.-520-1547A>G		intron	N/A	ENSP00000428716.1
	IDO1	ENST00000518804.5	TSL:4	c.-34-2033A>G		intron	N/A	ENSP00000429297.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88434 AN: 151912 Hom.: 27027 Cov.: 32

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.582 AC: 88523 AN: 152032 Hom.: 27069 Cov.: 32 AF XY: 0.572 AC XY: 42481 AN XY: 74318

African (AFR) AF: 0.770 AC: 31956 AN: 41482

American (AMR) AF: 0.492 AC: 7514 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1945 AN: 3470

East Asian (EAS) AF: 0.499 AC: 2572 AN: 5154

South Asian (SAS) AF: 0.325 AC: 1565 AN: 4822

European-Finnish (FIN) AF: 0.483 AC: 5104 AN: 10576

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35963 AN: 67950

Other (OTH) AF: 0.577 AC: 1215 AN: 2106

Alfa AF: 0.545 Hom.: 92001

Bravo AF: 0.597

Asia WGS AF: 0.415 AC: 1444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.29
PhyloP100		-0.60
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: rs3808606; hg19: chr8-39769375;