rs3824259

Positions:

• chr8-39912074-C-A
• chr8-39912074-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000517623.1(ENSG00000253939):​n.256-8053G>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 151,578 control chromosomes in the GnomAD database, including 28,159 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 0.59 (28159 hom., cov: 31)
• Consequence: ENST00000517623.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000517623.1	n.256-8053G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.593 AC: 89836 AN: 151478 Hom.: 28111 Cov.: 31

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.595

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.593 AC: 89932 AN: 151578 Hom.: 28159 Cov.: 31 AF XY: 0.583 AC XY: 43121 AN XY: 73980

Gnomad4 AFR AF: 0.804

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.592

Alfa AF: 0.557 Hom.: 4133

Bravo AF: 0.609

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.31

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

LitVar

Other links and lift over

dbSNP: rs3824259; hg19: chr8-39769593;