rs8192859

chr7-139994862-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001061.7(TBXAS1):c.1135-12229C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,232 control chromosomes in the GnomAD database, including 2,041 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 0.14 (2041 hom., cov: 32)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.799

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBXAS1	NM_001061.7	c.1135-12229C>T		intron_variant		ENST00000448866.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBXAS1	ENST00000448866.7	c.1135-12229C>T		intron_variant		1	NM_001061.7	P1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21998 AN: 152114 Hom.: 2040 Cov.: 32

Gnomad AFR AF: 0.0572

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.145 AC: 22009 AN: 152232 Hom.: 2041 Cov.: 32 AF XY: 0.141 AC XY: 10514 AN XY: 74430

Gnomad4 AFR AF: 0.0571

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.126

Alfa AF: 0.193 Hom.: 4243

Bravo AF: 0.130

Asia WGS AF: 0.0840 AC: 295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.7
Dann	Benign	0.59

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: rs8192859; hg19: chr7-139694661;