11-18038806-C-T

Variant summary

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

The NM_004179.3(TPH1):c.117+1840G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,742 control chromosomes in the GnomAD database, including 10,469 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 0.36 (10469 hom., cov: 32)
• Consequence: TPH1 NM_004179.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPH1	NM_004179.3	c.117+1840G>A		intron_variant		ENST00000682019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH1	ENST00000682019.1	c.117+1840G>A		intron_variant			NM_004179.3	P1
TPH1	ENST00000250018.6	c.117+1840G>A		intron_variant		1		P1
TPH1	ENST00000417164.5	c.117+1840G>A		intron_variant, NMD_transcript_variant		1
TPH1	ENST00000528338.1	c.147+1840G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54922 AN: 151624 Hom.: 10466 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.362 AC: 54948 AN: 151742 Hom.: 10469 Cov.: 32 AF XY: 0.365 AC XY: 27074 AN XY: 74164

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.367

Alfa AF: 0.382 Hom.: 1851

Bravo AF: 0.355

Asia WGS AF: 0.396 AC: 1370 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.086
Dann	Benign	0.41

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: rs684302; hg19: chr11-18060353;