rs1872824

Variant names:

• chr12-72036534-A-G
• rs1872824
• ENST00000547278.1:n.78+5143A>G

Variant summary

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

The ENST00000547278.1(TPH2):​n.78+5143A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,068 control chromosomes in the GnomAD database, including 24,264 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 0.54 (24264 hom., cov: 32)
• Consequence: TPH2 ENST00000547278.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000547278.1	n.78+5143A>G		intron_variant	Intron 1 of 5	3
TPH2	ENST00000547348.5	n.100+5143A>G		intron_variant	Intron 1 of 3	3
TPH2	ENST00000550403.5	n.120+5143A>G		intron_variant	Intron 1 of 5	3
TPH2	ENST00000551074.5	n.93+5143A>G		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82521 AN: 151948 Hom.: 24254 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.543 AC: 82559 AN: 152068 Hom.: 24264 Cov.: 32 AF XY: 0.546 AC XY: 40619 AN XY: 74330

African (AFR) AF: 0.302 AC: 12523 AN: 41494

American (AMR) AF: 0.597 AC: 9123 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2159 AN: 3472

East Asian (EAS) AF: 0.577 AC: 2980 AN: 5162

South Asian (SAS) AF: 0.551 AC: 2657 AN: 4818

European-Finnish (FIN) AF: 0.641 AC: 6773 AN: 10564

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44468 AN: 67964

Other (OTH) AF: 0.564 AC: 1186 AN: 2104

Alfa AF: 0.615 Hom.: 33288

Bravo AF: 0.525

Asia WGS AF: 0.523 AC: 1820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.62
DANN	Benign	0.60
PhyloP100		0.72

Splicing

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

Other links and lift over

dbSNP: rs1872824; hg19: chr12-72430314;