Variant 8-39927927-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002164.6(IDO1):c.954G>A(p.Glu318Glu) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.685

Variant links:

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]

IDO1 links:

IDO1 (HGNC:):

IDO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.685 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IDO1	NM_002164.6 linkuse as main transcript	c.954G>A	p.Glu318Glu	synonymous_variant	10/10	ENST00000518237.6	NP_002155.1	P14902A0A348GSI3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IDO1	ENST00000518237.6 linkuse as main transcript	c.954G>A	p.Glu318Glu	synonymous_variant	10/10	1	NM_002164.6	ENSP00000430950.1		P14902

Frequencies

GnomAD3 genomes

AF:

0.00279

AC:

425

AN:

152186

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00291

AC XY:

373

AN XY:

128322

show subpopulations

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.:

Cov.:

AF XY:

0.00392

AC XY:

2835

AN XY:

723196

show subpopulations

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.:

Cov.:

AF XY:

0.00270

AC XY:

201

AN XY:

74480

show subpopulations

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.:

Bravo

AF:

0.00288

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 25, 2018	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over