rs35099072

chr8-39918134-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002164.6(IDO1):c.230G>A(p.Arg77His) variant causes a missense change. The variant allele was found at a frequency of 0.00053 in 1,613,896 control chromosomes in the GnomAD database, including 7 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 0.0027 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (2 hom.)
• Consequence: IDO1 NM_002164.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01365599).
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IDO1	NM_002164.6	c.230G>A	p.Arg77His	missense_variant	3/10	ENST00000518237.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDO1	ENST00000518237.6	c.230G>A	p.Arg77His	missense_variant	3/10	1	NM_002164.6	P1
	ENST00000522970.1	n.547C>T		non_coding_transcript_exon_variant	2/2	3
	ENST00000517623.1	n.256-14113C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00273 AC: 416 AN: 152132 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00956

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000690 AC: 172 AN: 249202 Hom.: 1 AF XY: 0.000422 AC XY: 57 AN XY: 135198

Gnomad AFR exome AF: 0.0101

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000300 AC: 439 AN: 1461646 Hom.: 2 Cov.: 32 AF XY: 0.000242 AC XY: 176 AN XY: 727106

Gnomad4 AFR exome AF: 0.0108

Gnomad4 AMR exome AF: 0.000470

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000198

Gnomad4 OTH exome AF: 0.000547

GnomAD4 genome AF: 0.00273 AC: 416 AN: 152250 Hom.: 5 Cov.: 32 AF XY: 0.00261 AC XY: 194 AN XY: 74430

Gnomad4 AFR AF: 0.00953

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000586 Hom.: 2

Bravo AF: 0.00308

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00872 AC: 35

ESP6500EA AF: 0.000239 AC: 2

ExAC AF: 0.000860 AC: 104

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Uncertain	-0.080
Cadd	Uncertain	24
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.026	T;.;T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.68	T;T;.;D
MetaRNN	Benign	0.014	T;T;T;T
MetaSVM	Benign	-0.32	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.9	D;D;N;N
REVEL	Uncertain	0.41
Sift	Uncertain	0.029	D;T;T;T
Sift4G	Pathogenic	0.0	D;D;T;T
Polyphen		1.0	.;.;D;D
Vest4		0.35
MVP		0.72
MPC		0.29
ClinPred		0.063	T
GERP RS		5.7
Varity_R		0.27
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs35099072; hg19: chr8-39775653; COSMIC: COSV99503308; COSMIC: COSV99503308;