rs4760815

Variant names:

• chr12-71978449-T-A
• rs4760815
• NM_173353.4:c.806-503T>A

Variant summary

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

The NM_173353.4(TPH2):​c.806-503T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,954 control chromosomes in the GnomAD database, including 25,244 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 0.57 (25244 hom., cov: 31)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 4 publications found

Genes affected

TPH2 (HGNC:20692): (tryptophan hydroxylase 2) This gene encodes a member of the pterin-dependent aromatic 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 may be associated with psychiatric diseases such as bipolar affective disorder and major depression. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.806-503T>A		intron_variant	Intron 6 of 10	ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.806-503T>A		intron_variant	Intron 6 of 10	1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87169 AN: 151836 Hom.: 25223 Cov.: 31

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.574 AC: 87232 AN: 151954 Hom.: 25244 Cov.: 31 AF XY: 0.572 AC XY: 42480 AN XY: 74274

African (AFR) AF: 0.588 AC: 24352 AN: 41422

American (AMR) AF: 0.550 AC: 8398 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2176 AN: 3472

East Asian (EAS) AF: 0.473 AC: 2437 AN: 5156

South Asian (SAS) AF: 0.530 AC: 2550 AN: 4814

European-Finnish (FIN) AF: 0.566 AC: 5957 AN: 10534

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.579 AC: 39374 AN: 67970

Other (OTH) AF: 0.586 AC: 1238 AN: 2112

Alfa AF: 0.582 Hom.: 3190

Bravo AF: 0.575

Asia WGS AF: 0.499 AC: 1737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.58
PhyloP100		-0.047
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: rs4760815; hg19: chr12-72372229;