rs11606304

chr11-18030701-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004179.3(TPH1):c.403-1122A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0523 in 152,192 control chromosomes in the GnomAD database, including 293 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 0.052 (293 hom., cov: 32)
• Consequence: TPH1 NM_004179.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPH1	NM_004179.3	c.403-1122A>C		intron_variant		ENST00000682019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH1	ENST00000682019.1	c.403-1122A>C		intron_variant			NM_004179.3	P1
TPH1	ENST00000250018.6	c.403-1122A>C		intron_variant		1		P1
TPH1	ENST00000417164.5	c.403-1122A>C		intron_variant, NMD_transcript_variant		1
TPH1	ENST00000528338.1	c.433-1122A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0523 AC: 7956 AN: 152074 Hom.: 292 Cov.: 32

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0760

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0673

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0770

Gnomad OTH AF: 0.0398

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

GnomAD4 genome AF: 0.0523 AC: 7961 AN: 152192 Hom.: 293 Cov.: 32 AF XY: 0.0518 AC XY: 3856 AN XY: 74400

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.0761

Gnomad4 ASJ AF: 0.0207

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.0673

Gnomad4 NFE AF: 0.0770

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0686 Hom.: 149

Bravo AF: 0.0503

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.35
Dann	Benign	0.47

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: rs11606304; hg19: chr11-18052248;