12-72112507-G-T

Variant names:

• chr12-72112507-G-T
• rs2220159
• ENST00000547278.1:n.596+36799G>T

Variant summary

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

The ENST00000547278.1(TPH2):​n.596+36799G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,120 control chromosomes in the GnomAD database, including 44,013 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 0.76 (44013 hom., cov: 33)
• Consequence: TPH2 ENST00000547278.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• 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]

TRHDE (HGNC:30748): (thyrotropin releasing hormone degrading enzyme) This gene encodes a member of the peptidase M1 family. The encoded protein is an extracellular peptidase that specifically cleaves and inactivates the neuropeptide thyrotropin-releasing hormone.[provided by RefSeq, Dec 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000547278.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH2	ENST00000547278.1	TSL:3	n.596+36799G>T		intron	N/A
	TPH2	ENST00000547348.5	TSL:3	n.203-55031G>T		intron	N/A
	TRHDE	ENST00000548156.1	TSL:4	n.279+6755G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114798 AN: 152000 Hom.: 43980 Cov.: 33

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.755 AC: 114893 AN: 152120 Hom.: 44013 Cov.: 33 AF XY: 0.758 AC XY: 56361 AN XY: 74358

African (AFR) AF: 0.647 AC: 26852 AN: 41484

American (AMR) AF: 0.740 AC: 11300 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2685 AN: 3466

East Asian (EAS) AF: 0.643 AC: 3325 AN: 5168

South Asian (SAS) AF: 0.706 AC: 3404 AN: 4820

European-Finnish (FIN) AF: 0.864 AC: 9159 AN: 10596

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.819 AC: 55724 AN: 67998

Other (OTH) AF: 0.753 AC: 1591 AN: 2114

Alfa AF: 0.781 Hom.: 6042

Bravo AF: 0.739

Asia WGS AF: 0.643 AC: 2238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.71
DANN	Benign	0.21
PhyloP100		-0.21

Splicing

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

Other links and lift over

dbSNP: rs2220159; hg19: chr12-72506287;