chr8-40014064-G-C

Variant names:

• chr8-40014064-G-C
• rs4445211
• NM_194294.5:c.868+351G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194294.5(IDO2):​c.868+351G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,038 control chromosomes in the GnomAD database, including 11,583 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 0.38 (11583 hom., cov: 31)
• Consequence: IDO2 NM_194294.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• Publications: 2 publications found

Genes affected

IDO2 (HGNC:27269): (indoleamine 2,3-dioxygenase 2) Along with the enzymes encoded by the INDO (MIM 147435) and TDO2 (MIM 191070) genes, the enzyme encoded by the INDOL1 gene metabolizes tryptophan in the kynurenine pathway (Ball et al., 2007 [PubMed 17499941]).[supplied by OMIM, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194294.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDO2	NM_194294.5	MANE Select	c.868+351G>C		intron	N/A	NP_919270.3
	IDO2	NM_001395206.1		c.868+351G>C		intron	N/A	NP_001382135.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDO2	ENST00000502986.4	TSL:5 MANE Select	c.868+351G>C		intron	N/A	ENSP00000443432.2
	IDO2	ENST00000343295.8	TSL:2	n.3119+351G>C		intron	N/A
	IDO2	ENST00000418094.1	TSL:2	n.495+351G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58225 AN: 151922 Hom.: 11568 Cov.: 31

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.383 AC: 58271 AN: 152038 Hom.: 11583 Cov.: 31 AF XY: 0.383 AC XY: 28492 AN XY: 74328

African (AFR) AF: 0.400 AC: 16590 AN: 41486

American (AMR) AF: 0.515 AC: 7870 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1087 AN: 3466

East Asian (EAS) AF: 0.380 AC: 1961 AN: 5162

South Asian (SAS) AF: 0.300 AC: 1448 AN: 4822

European-Finnish (FIN) AF: 0.350 AC: 3699 AN: 10570

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24248 AN: 67948

Other (OTH) AF: 0.394 AC: 831 AN: 2108

Alfa AF: 0.231 Hom.: 506

Bravo AF: 0.404

Asia WGS AF: 0.358 AC: 1242 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs4445211; hg19: chr8-39871583;