rs1799913

Variant names:

• chr11-18025708-G-T
• rs1799913
• NM_004179.3:c.804-7C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-18025708-G-T
• chr11-18025708-G-A
• chr11-18025708-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_004179.3(TPH1):​c.804-7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,613,054 control chromosomes in the GnomAD database, including 123,521 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.34 (9477 hom., cov: 32)
  • Exomes 𝑓: 0.39 (114044 hom.)
• Consequence: TPH1 NM_004179.3 splice_region, intron
• Scores: Splicing: ADA: 0.0007345
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.630
• Publications: 89 publications found

Genes affected

TPH1 (HGNC:12008): (tryptophan hydroxylase 1) This gene encodes a member of the aromatic amino 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 have been associated with an elevated risk for a variety of diseases and disorders, including schizophrenia, somatic anxiety, anger-related traits, bipolar disorder, suicidal behavior, addictions, and others.[provided by RefSeq, Apr 2009]

ENSG00000302464 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-18025708-G-T is Benign according to our data. Variant chr11-18025708-G-T is described in ClinVar as Benign. ClinVar VariationId is 3060644.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004179.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH1	NM_004179.3	MANE Select	c.804-7C>A		splice_region intron	N/A	NP_004170.1	P17752-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH1	ENST00000682019.1	MANE Select	c.804-7C>A		splice_region intron	N/A	ENSP00000508368.1	P17752-1
	TPH1	ENST00000250018.6	TSL:1	c.804-7C>A		splice_region intron	N/A	ENSP00000250018.2	P17752-1
	TPH1	ENST00000417164.5	TSL:1	n.607-7C>A		splice_region intron	N/A	ENSP00000403831.1	E7EMX4

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51501 AN: 151950 Hom.: 9480 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.357

GnomAD2 exomes AF: 0.390 AC: 98099 AN: 251264 AF XY: 0.391

Gnomad AFR exome AF: 0.174

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.520

Gnomad EAS exome AF: 0.464

Gnomad FIN exome AF: 0.442

Gnomad NFE exome AF: 0.397

Gnomad OTH exome AF: 0.404

GnomAD4 exome AF: 0.391 AC: 571955 AN: 1460986 Hom.: 114044 Cov.: 41 AF XY: 0.391 AC XY: 284282 AN XY: 726840

African (AFR) AF: 0.170 AC: 5673 AN: 33448

American (AMR) AF: 0.400 AC: 17884 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 13645 AN: 26120

East Asian (EAS) AF: 0.484 AC: 19224 AN: 39686

South Asian (SAS) AF: 0.352 AC: 30368 AN: 86238

European-Finnish (FIN) AF: 0.440 AC: 23466 AN: 53382

Middle Eastern (MID) AF: 0.370 AC: 2134 AN: 5764

European-Non Finnish (NFE) AF: 0.392 AC: 436075 AN: 1111288

Other (OTH) AF: 0.389 AC: 23486 AN: 60356

GnomAD4 genome AF: 0.339 AC: 51503 AN: 152068 Hom.: 9477 Cov.: 32 AF XY: 0.343 AC XY: 25456 AN XY: 74316

African (AFR) AF: 0.180 AC: 7465 AN: 41508

American (AMR) AF: 0.383 AC: 5852 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1815 AN: 3468

East Asian (EAS) AF: 0.461 AC: 2387 AN: 5174

South Asian (SAS) AF: 0.336 AC: 1617 AN: 4810

European-Finnish (FIN) AF: 0.438 AC: 4622 AN: 10546

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26552 AN: 67966

Other (OTH) AF: 0.353 AC: 745 AN: 2110

Alfa AF: 0.374 Hom.: 26613

Bravo AF: 0.330

EpiCase AF: 0.389

EpiControl AF: 0.402

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TPH1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.4
DANN	Benign	0.70
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00073
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.20		Position offset: -7

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

Other links and lift over

dbSNP: rs1799913; hg19: chr11-18047255; COSMIC: COSV51457405; COSMIC: COSV51457405;