11-18027646-G-C

Variant names:

• chr11-18027646-G-C
• rs2237907
• NM_004179.3:c.668-1021C>G

Variant summary

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

The NM_004179.3(TPH1):​c.668-1021C>G 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 152,076 control chromosomes in the GnomAD database, including 9,508 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 (9508 hom., cov: 32)
• Consequence: TPH1 NM_004179.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 1 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 = 0.446 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH1	NM_004179.3	MANE Select	c.668-1021C>G		intron	N/A	NP_004170.1	P17752-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH1	ENST00000682019.1	MANE Select	c.668-1021C>G		intron	N/A	ENSP00000508368.1	P17752-1
	TPH1	ENST00000250018.6	TSL:1	c.668-1021C>G		intron	N/A	ENSP00000250018.2	P17752-1
	TPH1	ENST00000417164.5	TSL:1	n.471-1021C>G		intron	N/A	ENSP00000403831.1	E7EMX4

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51581 AN: 151958 Hom.: 9511 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.339 AC: 51583 AN: 152076 Hom.: 9508 Cov.: 32 AF XY: 0.343 AC XY: 25504 AN XY: 74318

African (AFR) AF: 0.180 AC: 7481 AN: 41494

American (AMR) AF: 0.384 AC: 5861 AN: 15278

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

East Asian (EAS) AF: 0.461 AC: 2388 AN: 5176

South Asian (SAS) AF: 0.337 AC: 1622 AN: 4816

European-Finnish (FIN) AF: 0.440 AC: 4638 AN: 10548

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

European-Non Finnish (NFE) AF: 0.391 AC: 26581 AN: 67974

Other (OTH) AF: 0.354 AC: 749 AN: 2114

Alfa AF: 0.182 Hom.: 407

Bravo AF: 0.330

Asia WGS AF: 0.372 AC: 1291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.79
PhyloP100		-0.093
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: rs2237907; hg19: chr11-18049193;