rs3735355

chr7-139957529-C-A

Variant summary

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

The NM_001061.7(TBXAS1):c.689-105C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0933 in 1,516,642 control chromosomes in the GnomAD database, including 7,759 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 0.079 (712 hom., cov: 31)
  • Exomes 𝑓: 0.095 (7047 hom.)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) 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.689-105C>A		intron_variant		ENST00000448866.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBXAS1	ENST00000448866.7	c.689-105C>A		intron_variant		1	NM_001061.7	P1

Frequencies

GnomAD3 genomes AF: 0.0792 AC: 12044 AN: 152030 Hom.: 712 Cov.: 31

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0556

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.0988

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0928

Gnomad OTH AF: 0.0788

GnomAD4 exome AF: 0.0949 AC: 129456 AN: 1364494 Hom.: 7047 AF XY: 0.0951 AC XY: 65017 AN XY: 683416

Gnomad4 AFR exome AF: 0.0159

Gnomad4 AMR exome AF: 0.0351

Gnomad4 ASJ exome AF: 0.0694

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.0957

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.0918

Gnomad4 OTH exome AF: 0.0916

GnomAD4 genome AF: 0.0791 AC: 12039 AN: 152148 Hom.: 712 Cov.: 31 AF XY: 0.0844 AC XY: 6274 AN XY: 74360

Gnomad4 AFR AF: 0.0184

Gnomad4 AMR AF: 0.0555

Gnomad4 ASJ AF: 0.0749

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.0985

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.0928

Gnomad4 OTH AF: 0.0794

Alfa AF: 0.0833 Hom.: 86

Bravo AF: 0.0654

Asia WGS AF: 0.138 AC: 480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.016
Dann	Benign	0.57

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: rs3735355; hg19: chr7-139657328; COSMIC: COSV54956691; COSMIC: COSV54956691;