rs10487661

chr7-139797880-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TBXAS1	NM_001130966.5	c.-80+10454C>T		intron_variant
TBXAS1	NM_001166254.4	c.-113+10454C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBXAS1	ENST00000336425.10	c.-80+10454C>T		intron_variant		1		P1
TBXAS1	ENST00000425687.5	c.-113+10454C>T		intron_variant		1
TBXAS1	ENST00000438104.6	c.-80+10454C>T		intron_variant		5

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

Gnomad4 AFR AF: 0.0756

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.0692

Gnomad4 FIN AF: 0.0415

Gnomad4 NFE AF: 0.0358

Gnomad4 OTH AF: 0.0724

Alfa AF: 0.0590 Hom.: 53

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10487661; hg19: chr7-139497679;