NM_002164.6:c.857-28G>A

Variant names:

• chr8-39927802-G-A
• rs3739319
• NM_002164.6:c.857-28G>A

Variant summary

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

The NM_002164.6(IDO1):​c.857-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 1,419,442 control chromosomes in the GnomAD database, including 114,592 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 0.38 (11218 hom., cov: 30)
  • Exomes 𝑓: 0.40 (103374 hom.)
• Consequence: IDO1 NM_002164.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDO1	NM_002164.6	c.857-28G>A		intron_variant	Intron 9 of 9	ENST00000518237.6	NP_002155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDO1	ENST00000518237.6	c.857-28G>A		intron_variant	Intron 9 of 9	1	NM_002164.6	ENSP00000430950.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57382 AN: 151692 Hom.: 11218 Cov.: 30

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.393

GnomAD2 exomes AF: 0.404 AC: 41684 AN: 103296 AF XY: 0.412

Gnomad AFR exome AF: 0.312

Gnomad AMR exome AF: 0.302

Gnomad ASJ exome AF: 0.473

Gnomad EAS exome AF: 0.550

Gnomad FIN exome AF: 0.395

Gnomad NFE exome AF: 0.394

Gnomad OTH exome AF: 0.421

GnomAD4 exome AF: 0.399 AC: 506283 AN: 1267630 Hom.: 103374 Cov.: 19 AF XY: 0.403 AC XY: 249376 AN XY: 618646

African (AFR) AF: 0.336 AC: 9459 AN: 28142

American (AMR) AF: 0.313 AC: 6928 AN: 22162

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 9099 AN: 18898

East Asian (EAS) AF: 0.551 AC: 19791 AN: 35924

South Asian (SAS) AF: 0.538 AC: 33273 AN: 61822

European-Finnish (FIN) AF: 0.403 AC: 18404 AN: 45640

Middle Eastern (MID) AF: 0.572 AC: 2940 AN: 5144

European-Non Finnish (NFE) AF: 0.386 AC: 384432 AN: 996986

Other (OTH) AF: 0.415 AC: 21957 AN: 52912

GnomAD4 genome AF: 0.378 AC: 57419 AN: 151812 Hom.: 11218 Cov.: 30 AF XY: 0.381 AC XY: 28275 AN XY: 74184

African (AFR) AF: 0.315 AC: 13030 AN: 41366

American (AMR) AF: 0.343 AC: 5236 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1694 AN: 3464

East Asian (EAS) AF: 0.556 AC: 2863 AN: 5146

South Asian (SAS) AF: 0.546 AC: 2619 AN: 4798

European-Finnish (FIN) AF: 0.380 AC: 3998 AN: 10532

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26653 AN: 67924

Other (OTH) AF: 0.393 AC: 829 AN: 2108

Alfa AF: 0.382 Hom.: 17670

Bravo AF: 0.371

Asia WGS AF: 0.514 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.31
PhyloP100		-2.6
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: rs3739319; hg19: chr8-39785321; COSMIC: COSV53712999; COSMIC: COSV53712999;