rs17794760

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TPH1	NM_004179.3	c.302-999C>T		intron_variant		ENST00000682019.1	NP_004170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPH1	ENST00000682019.1	c.302-999C>T		intron_variant			NM_004179.3	ENSP00000508368	P1
TPH1	ENST00000250018.6	c.302-999C>T		intron_variant		1		ENSP00000250018	P1
TPH1	ENST00000417164.5	c.302-999C>T		intron_variant, NMD_transcript_variant		1		ENSP00000403831
TPH1	ENST00000528338.1	c.332-999C>T		intron_variant		3		ENSP00000436081

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

Gnomad4 AFR AF: 0.0860

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.0987

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.153

Alfa AF: 0.172 Hom.: 3012

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

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: rs17794760; hg19: chr11-18055920;