rs7820268

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002164.6(IDO1):​c.423-90C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000099 in 1,010,608 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
Exomes 𝑓: 9.9e-7 ( 0 hom. )

Consequence

IDO1
NM_002164.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.291

Publications

0 publications found
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IDO1NM_002164.6 linkc.423-90C>A intron_variant Intron 4 of 9 ENST00000518237.6 NP_002155.1 P14902A0A348GSI3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IDO1ENST00000518237.6 linkc.423-90C>A intron_variant Intron 4 of 9 1 NM_002164.6 ENSP00000430950.1 P14902

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
9.90e-7
AC:
1
AN:
1010608
Hom.:
0
AF XY:
0.00000191
AC XY:
1
AN XY:
522420
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
24502
American (AMR)
AF:
0.00
AC:
0
AN:
42472
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23200
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37428
South Asian (SAS)
AF:
0.0000134
AC:
1
AN:
74828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51718
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4906
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
706064
Other (OTH)
AF:
0.00
AC:
0
AN:
45490
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
1.1
DANN
Benign
0.55
PhyloP100
-0.29

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

Publications

Other links and lift over

dbSNP: rs7820268; hg19: chr8-39777529; API