Variant chr11-18025708-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_004179.3(TPH1):c.804-7C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,613,054 control chromosomes in the GnomAD database, including 123,521 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.34 ( 9477 hom., cov: 32)

Exomes 𝑓: 0.39 ( 114044 hom. )

Consequence

TPH1
NM_004179.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0007345

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.630

Variant links:

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]

TPH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 11-18025708-G-T is Benign according to our data. Variant chr11-18025708-G-T is described in ClinVar as [Benign]. Clinvar id is 3060644.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH1	NM_004179.3 linkuse as main transcript	c.804-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000682019.1	NP_004170.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
TPH1	ENST00000682019.1 linkuse as main transcript	c.804-7C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NM_004179.3	ENSP00000508368	P1	P17752-1
TPH1	ENST00000250018.6 linkuse as main transcript	c.804-7C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000250018	P1	P17752-1
TPH1	ENST00000417164.5 linkuse as main transcript	c.607-7C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	1		ENSP00000403831

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51501

AN:

151950

Hom.:

9480

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.523

Gnomad EAS

AF:

0.462

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

GnomAD3 exomes

AF:

0.390

AC:

98099

AN:

251264

Hom.:

19785

AF XY:

0.391

AC XY:

53142

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.400

Gnomad ASJ exome

AF:

0.520

Gnomad EAS exome

AF:

0.464

Gnomad SAS exome

AF:

0.344

Gnomad FIN exome

AF:

0.442

Gnomad NFE exome

AF:

0.397

Gnomad OTH exome

AF:

0.404

GnomAD4 exome

AF:

0.391

AC:

571955

AN:

1460986

Hom.:

114044

Cov.:

AF XY:

0.391

AC XY:

284282

AN XY:

726840

show subpopulations

Gnomad4 AFR exome

AF:

0.170

Gnomad4 AMR exome

AF:

0.400

Gnomad4 ASJ exome

AF:

0.522

Gnomad4 EAS exome

AF:

0.484

Gnomad4 SAS exome

AF:

0.352

Gnomad4 FIN exome

AF:

0.440

Gnomad4 NFE exome

AF:

0.392

Gnomad4 OTH exome

AF:

0.389

GnomAD4 genome

AF:

0.339

AC:

51503

AN:

152068

Hom.:

9477

Cov.:

AF XY:

0.343

AC XY:

25456

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.383

Gnomad4 ASJ

AF:

0.523

Gnomad4 EAS

AF:

0.461

Gnomad4 SAS

AF:

0.336

Gnomad4 FIN

AF:

0.438

Gnomad4 NFE

AF:

0.391

Gnomad4 OTH

AF:

0.353

Alfa

AF:

0.369

Hom.:

6911

Bravo

AF:

0.330

EpiCase

AF:

0.389

EpiControl

AF:

0.402

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TPH1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.4

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00073

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.20

Position offset: -7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over