11-18042860-A-G

Variant names:

• chr11-18042860-A-G
• rs652458
• NM_004179.3:c.-26-2072T>C

Variant summary

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

The NM_004179.3(TPH1):​c.-26-2072T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,104 control chromosomes in the GnomAD database, including 10,530 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 0.36 (10530 hom., cov: 33)
• Consequence: TPH1 NM_004179.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 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.-26-2072T>C		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.-26-2072T>C		intron	N/A	ENSP00000508368.1	P17752-1
	TPH1	ENST00000858102.1		c.-26-2072T>C		intron	N/A	ENSP00000528161.1
	TPH1	ENST00000858103.1		c.-116-434T>C		intron	N/A	ENSP00000528162.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55104 AN: 151986 Hom.: 10523 Cov.: 33

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.363 AC: 55139 AN: 152104 Hom.: 10530 Cov.: 33 AF XY: 0.365 AC XY: 27177 AN XY: 74358

African (AFR) AF: 0.238 AC: 9859 AN: 41504

American (AMR) AF: 0.397 AC: 6065 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1854 AN: 3468

East Asian (EAS) AF: 0.514 AC: 2659 AN: 5178

South Asian (SAS) AF: 0.345 AC: 1667 AN: 4826

European-Finnish (FIN) AF: 0.440 AC: 4647 AN: 10570

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27167 AN: 67960

Other (OTH) AF: 0.366 AC: 773 AN: 2110

Alfa AF: 0.381 Hom.: 1434

Bravo AF: 0.356

Asia WGS AF: 0.400 AC: 1386 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.66
PhyloP100		-0.40
PromoterAI		-0.00040	Neutral

Splicing

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

Other links and lift over

dbSNP: rs652458; hg19: chr11-18064407;