rs17794760

Variant names:

• chr11-18034373-G-A
• rs17794760
• NM_004179.3:c.302-999C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-18034373-G-A
• chr11-18034373-G-C

Variant summary

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

The NM_004179.3(TPH1):​c.302-999C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,212 control chromosomes in the GnomAD database, including 1,740 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 0.14 (1740 hom., cov: 32)
• Consequence: TPH1 NM_004179.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 9 publications found

Genes affected

TPH1 (HGNC:12008): (tryptophan hydroxylase 1) This gene encodes a member of the aromatic amino acid hydroxylase family. The encoded protein catalyzes the first and rate limiting step in the biosynthesis of serotonin, an important hormone and neurotransmitter. Mutations in this gene have been associated with an elevated risk for a variety of diseases and disorders, including schizophrenia, somatic anxiety, anger-related traits, bipolar disorder, suicidal behavior, addictions, and others.[provided by RefSeq, Apr 2009]

ENSG00000302464 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH1	NM_004179.3	c.302-999C>T		intron_variant	Intron 3 of 10	ENST00000682019.1	NP_004170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH1	ENST00000682019.1	c.302-999C>T		intron_variant	Intron 3 of 10		NM_004179.3	ENSP00000508368.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21680 AN: 152094 Hom.: 1740 Cov.: 32

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0985

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.143 AC: 21696 AN: 152212 Hom.: 1740 Cov.: 32 AF XY: 0.137 AC XY: 10198 AN XY: 74440

African (AFR) AF: 0.0860 AC: 3571 AN: 41534

American (AMR) AF: 0.162 AC: 2484 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3470

East Asian (EAS) AF: 0.0987 AC: 512 AN: 5186

South Asian (SAS) AF: 0.156 AC: 752 AN: 4820

European-Finnish (FIN) AF: 0.103 AC: 1097 AN: 10602

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12276 AN: 67986

Other (OTH) AF: 0.153 AC: 323 AN: 2112

Alfa AF: 0.169 Hom.: 3751

Bravo AF: 0.143

Asia WGS AF: 0.144 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.76
PhyloP100		-0.15
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: rs17794760; hg19: chr11-18055920;