11-18024440-G-A

Variant names:

• chr11-18024440-G-A
• rs7933505
• NM_004179.3:c.931-457C>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.931-457C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,076 control chromosomes in the GnomAD database, including 8,938 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 0.31 (8938 hom., cov: 32)
• Consequence: TPH1 NM_004179.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991
• Publications: 12 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004179.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH1	NM_004179.3	MANE Select	c.931-457C>T		intron	N/A	NP_004170.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH1	ENST00000682019.1	MANE Select	c.931-457C>T		intron	N/A	ENSP00000508368.1
	TPH1	ENST00000250018.6	TSL:1	c.931-457C>T		intron	N/A	ENSP00000250018.2
	TPH1	ENST00000417164.5	TSL:1	n.*113-457C>T		intron	N/A	ENSP00000403831.1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47673 AN: 151958 Hom.: 8939 Cov.: 32

Gnomad AFR AF: 0.0906

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.313 AC: 47671 AN: 152076 Hom.: 8938 Cov.: 32 AF XY: 0.318 AC XY: 23682 AN XY: 74358

African (AFR) AF: 0.0904 AC: 3754 AN: 41528

American (AMR) AF: 0.374 AC: 5713 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1813 AN: 3464

East Asian (EAS) AF: 0.467 AC: 2409 AN: 5162

South Asian (SAS) AF: 0.336 AC: 1621 AN: 4822

European-Finnish (FIN) AF: 0.439 AC: 4625 AN: 10546

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26583 AN: 67968

Other (OTH) AF: 0.335 AC: 706 AN: 2108

Alfa AF: 0.366 Hom.: 29167

Bravo AF: 0.301

Asia WGS AF: 0.368 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.050
DANN	Benign	0.71
PhyloP100		-0.99
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: rs7933505; hg19: chr11-18045987;