8-39927927-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_002164.6(IDO1):c.954G>A(p.Glu318=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00387 in 1,607,732 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (24 hom.)
• Consequence: IDO1 NM_002164.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.685

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 8-39927927-G-A is Benign according to our data. Variant chr8-39927927-G-A is described in ClinVar as [Benign]. Clinvar id is 718318.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.685 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IDO1	NM_002164.6	c.954G>A	p.Glu318=	synonymous_variant	10/10	ENST00000518237.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDO1	ENST00000518237.6	c.954G>A	p.Glu318=	synonymous_variant	10/10	1	NM_002164.6	P1
	ENST00000517623.1	n.256-23906C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00279 AC: 425 AN: 152186 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00472

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00282 AC: 670 AN: 237440 Hom.: 1 AF XY: 0.00291 AC XY: 373 AN XY: 128322

Gnomad AFR exome AF: 0.000763

Gnomad AMR exome AF: 0.00157

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000139

Gnomad FIN exome AF: 0.00285

Gnomad NFE exome AF: 0.00486

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00398 AC: 5796 AN: 1455428 Hom.: 24 Cov.: 31 AF XY: 0.00392 AC XY: 2835 AN XY: 723196

Gnomad4 AFR exome AF: 0.000808

Gnomad4 AMR exome AF: 0.00158

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000142

Gnomad4 FIN exome AF: 0.00296

Gnomad4 NFE exome AF: 0.00475

Gnomad4 OTH exome AF: 0.00395

GnomAD4 genome AF: 0.00278 AC: 423 AN: 152304 Hom.: 1 Cov.: 32 AF XY: 0.00270 AC XY: 201 AN XY: 74480

Gnomad4 AFR AF: 0.000939

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.00469

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00380 Hom.: 4

Bravo AF: 0.00288

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 25, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	4.2
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs75174100; hg19: chr8-39785446;