rs4760750

Positions:

• chr12-71984109-A-C
• chr12-71984109-A-G

Variant summary

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

The NM_173353.4(TPH2):​c.941+5022A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,026 control chromosomes in the GnomAD database, including 25,791 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 0.58 (25791 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPH2	NM_173353.4	c.941+5022A>C		intron_variant		ENST00000333850.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000333850.4	c.941+5022A>C		intron_variant		1	NM_173353.4	P1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88055 AN: 151908 Hom.: 25765 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.580 AC: 88124 AN: 152026 Hom.: 25791 Cov.: 32 AF XY: 0.577 AC XY: 42885 AN XY: 74316

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.590

Alfa AF: 0.456 Hom.: 1211

Bravo AF: 0.581

Asia WGS AF: 0.501 AC: 1743 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	1.8
DANN	Benign	0.29

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: rs4760750; hg19: chr12-72377889;