11-18045114-G-T

Variant names:

• chr11-18045114-G-T
• rs7122118
• NM_004179.3:c.-27+1127C>A

Variant summary

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

The NM_004179.3(TPH1):​c.-27+1127C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,002 control chromosomes in the GnomAD database, including 17,791 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 0.47 (17791 hom., cov: 32)
• Consequence: TPH1 NM_004179.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 3 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 (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH1	NM_004179.3	c.-27+1127C>A		intron_variant	Intron 1 of 10	ENST00000682019.1	NP_004170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH1	ENST00000682019.1	c.-27+1127C>A		intron_variant	Intron 1 of 10		NM_004179.3	ENSP00000508368.1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70702 AN: 151884 Hom.: 17751 Cov.: 32

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.466 AC: 70793 AN: 152002 Hom.: 17791 Cov.: 32 AF XY: 0.457 AC XY: 33958 AN XY: 74294

African (AFR) AF: 0.655 AC: 27131 AN: 41448

American (AMR) AF: 0.365 AC: 5568 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1096 AN: 3464

East Asian (EAS) AF: 0.233 AC: 1202 AN: 5168

South Asian (SAS) AF: 0.343 AC: 1656 AN: 4822

European-Finnish (FIN) AF: 0.386 AC: 4079 AN: 10560

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28579 AN: 67954

Other (OTH) AF: 0.453 AC: 955 AN: 2110

Alfa AF: 0.265 Hom.: 584

Bravo AF: 0.474

Asia WGS AF: 0.320 AC: 1121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.49
PhyloP100		0.094

Splicing

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

Other links and lift over

dbSNP: rs7122118; hg19: chr11-18066661;