rs12667080

Positions:

• chr7-139825413-G-A

Variant summary

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

The ENST00000336425.10(TBXAS1):​c.-79-3899G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0946 in 152,204 control chromosomes in the GnomAD database, including 929 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 0.095 (929 hom., cov: 32)
• Consequence: TBXAS1 ENST00000336425.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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 (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBXAS1	NM_001130966.5	c.-79-3899G>A		intron_variant
TBXAS1	NM_001166254.4	c.-113+37987G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBXAS1	ENST00000336425.10	c.-79-3899G>A		intron_variant		1		P1
TBXAS1	ENST00000425687.5	c.-113+37987G>A		intron_variant		1
TBXAS1	ENST00000438104.6	c.-79-3899G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0948 AC: 14419 AN: 152086 Hom.: 929 Cov.: 32

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0657

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.0801

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

GnomAD4 genome AF: 0.0946 AC: 14406 AN: 152204 Hom.: 929 Cov.: 32 AF XY: 0.0913 AC XY: 6791 AN XY: 74412

Gnomad4 AFR AF: 0.0236

Gnomad4 AMR AF: 0.0656

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.0783

Alfa AF: 0.127 Hom.: 1941

Bravo AF: 0.0873

Asia WGS AF: 0.130 AC: 454 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	10
DANN	Benign	0.73

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: rs12667080; hg19: chr7-139525212;