rs7820268

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-39920010-C-A
• chr8-39920010-C-G
• chr8-39920010-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 0 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: 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
IDO1	NM_002164.6	c.423-90C>A		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>A		intron_variant	Intron 4 of 9	1	NM_002164.6	ENSP00000430950.1

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

⚠️ 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.

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

Other links and lift over

dbSNP: rs7820268; hg19: chr8-39777529;