11-18027646-G-C

Position:

• chr11-18027646-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH1	NM_004179.3	c.668-1021C>G		intron_variant		ENST00000682019.1	NP_004170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPH1	ENST00000682019.1	c.668-1021C>G		intron_variant			NM_004179.3	ENSP00000508368.1
TPH1	ENST00000250018.6	c.668-1021C>G		intron_variant		1		ENSP00000250018.2
TPH1	ENST00000417164.5	n.471-1021C>G		intron_variant		1		ENSP00000403831.1

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

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.354

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs2237907; hg19: chr11-18049193;