rs13152449

chr4-155914650-A-G

Variant summary

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

The NM_005651.4(TDO2):c.838+216A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,178 control chromosomes in the GnomAD database, including 946 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 0.10 (946 hom., cov: 32)
• Consequence: TDO2 NM_005651.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

Genes affected

TDO2 (HGNC:11708): (tryptophan 2,3-dioxygenase) This gene encodes a heme enzyme that plays a critical role in tryptophan metabolism by catalyzing the first and rate-limiting step of the kynurenine pathway. Increased activity of the encoded protein and subsequent kynurenine production may also play a role in cancer through the suppression of antitumor immune responses, and single nucleotide polymorphisms in this gene may be associated with autism. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDO2	NM_005651.4	c.838+216A>G		intron_variant		ENST00000536354.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDO2	ENST00000536354.3	c.838+216A>G		intron_variant		1	NM_005651.4	P1
TDO2	ENST00000512584.5	n.2348+216A>G		intron_variant, non_coding_transcript_variant		1
TDO2	ENST00000510293.1	n.94+216A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15939 AN: 152060 Hom.: 944 Cov.: 32

Gnomad AFR AF: 0.0936

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0741

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0995

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

GnomAD4 genome AF: 0.105 AC: 15948 AN: 152178 Hom.: 946 Cov.: 32 AF XY: 0.107 AC XY: 7945 AN XY: 74408

Gnomad4 AFR AF: 0.0936

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.0743

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.101

Alfa AF: 0.107 Hom.: 183

Bravo AF: 0.102

Asia WGS AF: 0.136 AC: 472 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.51
Dann	Benign	0.37

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: rs13152449; hg19: chr4-156835802;