11-18026269-G-T

Variant names:

• chr11-18026269-G-T
• rs1800532
• NM_004179.3:c.803+221C>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.803+221C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,680 control chromosomes in the GnomAD database, including 9,447 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 0.34 (9447 hom., cov: 30)
• Consequence: TPH1 NM_004179.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 181 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 (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH1	NM_004179.3	c.803+221C>A		intron_variant	Intron 7 of 10	ENST00000682019.1	NP_004170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH1	ENST00000682019.1	c.803+221C>A		intron_variant	Intron 7 of 10		NM_004179.3	ENSP00000508368.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51392 AN: 151566 Hom.: 9450 Cov.: 30

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.339 AC: 51393 AN: 151680 Hom.: 9447 Cov.: 30 AF XY: 0.343 AC XY: 25396 AN XY: 74102

African (AFR) AF: 0.180 AC: 7429 AN: 41358

American (AMR) AF: 0.382 AC: 5826 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1815 AN: 3470

East Asian (EAS) AF: 0.463 AC: 2390 AN: 5162

South Asian (SAS) AF: 0.336 AC: 1614 AN: 4800

European-Finnish (FIN) AF: 0.438 AC: 4584 AN: 10464

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

European-Non Finnish (NFE) AF: 0.391 AC: 26543 AN: 67884

Other (OTH) AF: 0.353 AC: 744 AN: 2106

Alfa AF: 0.344 Hom.: 8816

Bravo AF: 0.330

Asia WGS AF: 0.373 AC: 1295 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	0.15
DANN	Benign	0.72
PhyloP100		-1.3
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: rs1800532; hg19: chr11-18047816;