rs10487661

Variant names:

• chr7-139797880-C-T
• rs10487661
• ENST00000336425.10:c.-80+10454C>T

Variant summary

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

The ENST00000336425.10(TBXAS1):​c.-80+10454C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 152,244 control chromosomes in the GnomAD database, including 643 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 0.069 (643 hom., cov: 32)
• Consequence: TBXAS1 ENST00000336425.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 2 publications found

Genes affected

TBXAS1 (HGNC:11609): (thromboxane A synthase 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostglandin H2 to thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation. The enzyme plays a role in several pathophysiological processes including hemostasis, cardiovascular disease, and stroke. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

TBXAS1 Gene-Disease associations (from GenCC):

• ghosal hematodiaphyseal dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXAS1	NM_001130966.5	c.-80+10454C>T		intron_variant	Intron 4 of 16		NP_001124438.2
TBXAS1	NM_001166254.4	c.-113+10454C>T		intron_variant	Intron 3 of 14		NP_001159726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXAS1	ENST00000336425.10	c.-80+10454C>T		intron_variant	Intron 4 of 16	1		ENSP00000338087.7
TBXAS1	ENST00000425687.5	c.-113+10454C>T		intron_variant	Intron 3 of 14	1		ENSP00000388736.1
TBXAS1	ENST00000438104.6	c.-80+10454C>T		intron_variant	Intron 2 of 6	5		ENSP00000388612.3

Frequencies

GnomAD3 genomes AF: 0.0689 AC: 10475 AN: 152126 Hom.: 637 Cov.: 32

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.0415

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0703

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

GnomAD4 genome AF: 0.0690 AC: 10507 AN: 152244 Hom.: 643 Cov.: 32 AF XY: 0.0726 AC XY: 5400 AN XY: 74430

African (AFR) AF: 0.0756 AC: 3141 AN: 41534

American (AMR) AF: 0.182 AC: 2775 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3472

East Asian (EAS) AF: 0.209 AC: 1078 AN: 5170

South Asian (SAS) AF: 0.0692 AC: 334 AN: 4828

European-Finnish (FIN) AF: 0.0415 AC: 440 AN: 10614

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0358 AC: 2433 AN: 68026

Other (OTH) AF: 0.0724 AC: 153 AN: 2114

Alfa AF: 0.0555 Hom.: 626

Bravo AF: 0.0832

Asia WGS AF: 0.137 AC: 478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.21
DANN	Benign	0.37
PhyloP100		-1.2
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: rs10487661; hg19: chr7-139497679;