rs11179071

Variant names:

• chr12-72061405-G-A
• rs11179071
• ENST00000547278.1:n.241-12188G>A

Variant summary

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

The ENST00000547278.1(TPH2):​n.241-12188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 151,932 control chromosomes in the GnomAD database, including 2,042 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 0.16 (2042 hom., cov: 32)
• Consequence: TPH2 ENST00000547278.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 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.241-12188G>A		intron_variant	Intron 3 of 5	3
TPH2	ENST00000547348.5	n.202+13748G>A		intron_variant	Intron 2 of 3	3
TPH2	ENST00000550403.5	n.121-12188G>A		intron_variant	Intron 1 of 5	3
TPH2	ENST00000551074.5	n.195+13748G>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24175 AN: 151814 Hom.: 2047 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.159 AC: 24173 AN: 151932 Hom.: 2042 Cov.: 32 AF XY: 0.158 AC XY: 11734 AN XY: 74256

African (AFR) AF: 0.142 AC: 5905 AN: 41448

American (AMR) AF: 0.213 AC: 3249 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 696 AN: 3466

East Asian (EAS) AF: 0.233 AC: 1206 AN: 5166

South Asian (SAS) AF: 0.179 AC: 864 AN: 4816

European-Finnish (FIN) AF: 0.122 AC: 1282 AN: 10536

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.151 AC: 10265 AN: 67940

Other (OTH) AF: 0.177 AC: 374 AN: 2110

Alfa AF: 0.153 Hom.: 236

Bravo AF: 0.168

Asia WGS AF: 0.203 AC: 705 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.043
DANN	Benign	0.45
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs11179071; hg19: chr12-72455185;