chr8-39908329-C-T

Position:

• chr8-39908329-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000518804.5(IDO1):​c.-204-850C>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 ENST00000518804.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
		n.39908329C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IDO1	ENST00000522495.5	c.-182-4672C>T		intron_variant		5		ENSP00000430505.1
IDO1	ENST00000519154.5	c.-520-5074C>T		intron_variant		5		ENSP00000428716.1
IDO1	ENST00000518804.5	c.-204-850C>T		intron_variant		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

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.598

Alfa AF: 0.585 Hom.: 3288

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs9657182; hg19: chr8-39765848;