4-155910292-G-T

Position:

• chr4-155910292-G-T

Variant summary

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

The ENST00000536354.3(TDO2):​c.618+81G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,101,874 control chromosomes in the GnomAD database, including 11,038 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 0.18 (3281 hom., cov: 30)
  • Exomes 𝑓: 0.12 (7757 hom.)
• Consequence: TDO2 ENST00000536354.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDO2	NM_005651.4	c.618+81G>T		intron_variant		ENST00000536354.3	NP_005642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDO2	ENST00000536354.3	c.618+81G>T		intron_variant		1	NM_005651.4	ENSP00000444788	P1
TDO2	ENST00000512584.5	n.2128+81G>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27321 AN: 151678 Hom.: 3275 Cov.: 30

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.117 AC: 111246 AN: 950078 Hom.: 7757 AF XY: 0.120 AC XY: 57913 AN XY: 483760

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.0986

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.180 AC: 27357 AN: 151796 Hom.: 3281 Cov.: 30 AF XY: 0.181 AC XY: 13445 AN XY: 74184

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.176

Alfa AF: 0.107 Hom.: 718

Bravo AF: 0.186

Asia WGS AF: 0.224 AC: 777 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.010
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: rs10517626; hg19: chr4-156831444;