rs1487275

Variant names:

• chr12-72016512-C-A
• rs1487275
• NM_173353.4:c.1069-5887C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-72016512-C-A
• chr12-72016512-C-G
• chr12-72016512-C-T

Variant summary

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

The NM_173353.4(TPH2):​c.1069-5887C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 151,816 control chromosomes in the GnomAD database, including 37,837 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 0.70 (37837 hom., cov: 30)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527
• Publications: 23 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.1069-5887C>A		intron_variant	Intron 8 of 10	ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.1069-5887C>A		intron_variant	Intron 8 of 10	1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.705 AC: 106903 AN: 151696 Hom.: 37791 Cov.: 30

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.705 AC: 107013 AN: 151816 Hom.: 37837 Cov.: 30 AF XY: 0.702 AC XY: 52054 AN XY: 74180

African (AFR) AF: 0.725 AC: 30001 AN: 41380

American (AMR) AF: 0.699 AC: 10680 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2355 AN: 3470

East Asian (EAS) AF: 0.657 AC: 3359 AN: 5116

South Asian (SAS) AF: 0.644 AC: 3095 AN: 4808

European-Finnish (FIN) AF: 0.619 AC: 6509 AN: 10510

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48648 AN: 67944

Other (OTH) AF: 0.700 AC: 1477 AN: 2110

Alfa AF: 0.713 Hom.: 76680

Bravo AF: 0.710

Asia WGS AF: 0.635 AC: 2210 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.50
PhyloP100		-0.53
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: rs1487275; hg19: chr12-72410292;