8-39920010-C-T

Variant names:

• chr8-39920010-C-T
• rs7820268
• NM_002164.6:c.423-90C>T

Variant summary

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

The NM_002164.6(IDO1):​c.423-90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,160,248 control chromosomes in the GnomAD database, including 57,683 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 0.28 (6393 hom., cov: 33)
  • Exomes 𝑓: 0.31 (51290 hom.)
• Consequence: IDO1 NM_002164.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 34 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDO1	NM_002164.6	c.423-90C>T		intron_variant	Intron 4 of 9	ENST00000518237.6	NP_002155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDO1	ENST00000518237.6	c.423-90C>T		intron_variant	Intron 4 of 9	1	NM_002164.6	ENSP00000430950.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42745 AN: 151956 Hom.: 6389 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.312 AC: 314146 AN: 1008174 Hom.: 51290 AF XY: 0.309 AC XY: 160999 AN XY: 521212

African (AFR) AF: 0.219 AC: 5353 AN: 24438

American (AMR) AF: 0.161 AC: 6822 AN: 42424

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 8767 AN: 23162

East Asian (EAS) AF: 0.183 AC: 6837 AN: 37402

South Asian (SAS) AF: 0.192 AC: 14358 AN: 74746

European-Finnish (FIN) AF: 0.283 AC: 14603 AN: 51644

Middle Eastern (MID) AF: 0.356 AC: 1743 AN: 4898

European-Non Finnish (NFE) AF: 0.343 AC: 241407 AN: 704060

Other (OTH) AF: 0.314 AC: 14256 AN: 45400

GnomAD4 genome AF: 0.281 AC: 42755 AN: 152074 Hom.: 6393 Cov.: 33 AF XY: 0.275 AC XY: 20439 AN XY: 74328

African (AFR) AF: 0.218 AC: 9049 AN: 41452

American (AMR) AF: 0.218 AC: 3339 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1369 AN: 3472

East Asian (EAS) AF: 0.233 AC: 1207 AN: 5172

South Asian (SAS) AF: 0.188 AC: 905 AN: 4826

European-Finnish (FIN) AF: 0.261 AC: 2752 AN: 10564

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.339 AC: 23079 AN: 67986

Other (OTH) AF: 0.300 AC: 634 AN: 2116

Alfa AF: 0.321 Hom.: 32043

Bravo AF: 0.277

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.55
PhyloP100		-0.29
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: rs7820268; hg19: chr8-39777529; COSMIC: COSV53713442; COSMIC: COSV53713442;