rs4760820

chr12-72003216-C-G

Variant summary

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

The NM_173353.4(TPH2):c.1068+8651C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,900 control chromosomes in the GnomAD database, including 8,201 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 0.29 (8201 hom., cov: 31)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPH2	NM_173353.4	c.1068+8651C>G		intron_variant		ENST00000333850.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000333850.4	c.1068+8651C>G		intron_variant		1	NM_173353.4	P1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44439 AN: 151784 Hom.: 8199 Cov.: 31

Gnomad AFR AF: 0.0917

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.0964

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.293 AC: 44440 AN: 151900 Hom.: 8201 Cov.: 31 AF XY: 0.290 AC XY: 21524 AN XY: 74226

Gnomad4 AFR AF: 0.0917

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.0967

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.334

Alfa AF: 0.358 Hom.: 1596

Bravo AF: 0.278

Asia WGS AF: 0.147 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	16
Dann	Benign	0.60

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: rs4760820; hg19: chr12-72396996;