rs211107

Variant names:

• chr11-18036794-C-A
• rs211107
• NM_004179.3:c.118-652G>T

Variant summary

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

The NM_004179.3(TPH1):​c.118-652G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,988 control chromosomes in the GnomAD database, including 10,434 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 (10434 hom., cov: 31)
• Consequence: TPH1 NM_004179.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• Publications: 11 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH1	NM_004179.3	c.118-652G>T		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.118-652G>T		intron_variant	Intron 2 of 10		NM_004179.3	ENSP00000508368.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54793 AN: 151870 Hom.: 10431 Cov.: 31

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.361 AC: 54815 AN: 151988 Hom.: 10434 Cov.: 31 AF XY: 0.364 AC XY: 27013 AN XY: 74274

African (AFR) AF: 0.232 AC: 9635 AN: 41452

American (AMR) AF: 0.396 AC: 6036 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1843 AN: 3470

East Asian (EAS) AF: 0.507 AC: 2624 AN: 5178

South Asian (SAS) AF: 0.344 AC: 1660 AN: 4822

European-Finnish (FIN) AF: 0.443 AC: 4663 AN: 10534

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27134 AN: 67968

Other (OTH) AF: 0.366 AC: 770 AN: 2106

Alfa AF: 0.394 Hom.: 46662

Bravo AF: 0.354

Asia WGS AF: 0.396 AC: 1376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.4
DANN	Benign	0.64
PhyloP100		0.30
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: rs211107; hg19: chr11-18058341;