rs4725563

Positions:

• chr7-139954457-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.539+1001C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 152,146 control chromosomes in the GnomAD database, including 42,842 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 0.75 (42842 hom., cov: 32)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.844

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBXAS1	NM_001061.7	c.539+1001C>T		intron_variant		ENST00000448866.7	NP_001052.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBXAS1	ENST00000448866.7	c.539+1001C>T		intron_variant		1	NM_001061.7	ENSP00000402536	P1

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113771 AN: 152028 Hom.: 42807 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.748 AC: 113852 AN: 152146 Hom.: 42842 Cov.: 32 AF XY: 0.744 AC XY: 55334 AN XY: 74368

Gnomad4 AFR AF: 0.698

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.741

Alfa AF: 0.768 Hom.: 30544

Bravo AF: 0.756

Asia WGS AF: 0.733 AC: 2544 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.26
DANN	Benign	0.76

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: rs4725563; hg19: chr7-139654256;