11-18038806-C-T

Variant names:

• chr11-18038806-C-T
• rs684302
• NM_004179.3:c.117+1840G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.99).
• 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 rank	MANE	Protein	UniProt
TPH1	NM_004179.3	c.117+1840G>A		intron_variant	Intron 2 of 10	ENST00000682019.1	NP_004170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH1	ENST00000682019.1	c.117+1840G>A		intron_variant	Intron 2 of 10		NM_004179.3	ENSP00000508368.1

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

African (AFR) AF: 0.236 AC: 9773 AN: 41342

American (AMR) AF: 0.397 AC: 6046 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1841 AN: 3470

East Asian (EAS) AF: 0.510 AC: 2633 AN: 5164

South Asian (SAS) AF: 0.346 AC: 1663 AN: 4804

European-Finnish (FIN) AF: 0.442 AC: 4653 AN: 10520

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.399 AC: 27114 AN: 67886

Other (OTH) AF: 0.367 AC: 773 AN: 2108

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
PhyloP100		-2.3
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: rs684302; hg19: chr11-18060353;