rs2284212

chr7-139995517-G-Achr7-139995517-G-T

Variant summary

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

The NM_001061.7(TBXAS1):c.1135-11574G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,902 control chromosomes in the GnomAD database, including 10,332 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 0.35 (10332 hom., cov: 31)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBXAS1	NM_001061.7	c.1135-11574G>A		intron_variant		ENST00000448866.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBXAS1	ENST00000448866.7	c.1135-11574G>A		intron_variant		1	NM_001061.7	P1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53210 AN: 151784 Hom.: 10311 Cov.: 31

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.351 AC: 53267 AN: 151902 Hom.: 10332 Cov.: 31 AF XY: 0.346 AC XY: 25690 AN XY: 74232

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.342

Alfa AF: 0.296 Hom.: 7175

Bravo AF: 0.358

Asia WGS AF: 0.390 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.5
Dann	Benign	0.78

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: rs2284212; hg19: chr7-139695316;