7-139994701-C-T

Variant names:

• chr7-139994701-C-T
• rs3801148
• NM_001061.7:c.1135-12390C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001061.7(TBXAS1):​c.1135-12390C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,082 control chromosomes in the GnomAD database, including 14,401 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 0.40 (14401 hom., cov: 32)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 6 publications found

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]

TBXAS1 Gene-Disease associations (from GenCC):

• ghosal hematodiaphyseal dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXAS1	NM_001061.7	c.1135-12390C>T		intron_variant	Intron 9 of 12	ENST00000448866.7	NP_001052.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXAS1	ENST00000448866.7	c.1135-12390C>T		intron_variant	Intron 9 of 12	1	NM_001061.7	ENSP00000402536.3

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60931 AN: 151964 Hom.: 14396 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.401 AC: 60941 AN: 152082 Hom.: 14401 Cov.: 32 AF XY: 0.406 AC XY: 30206 AN XY: 74314

African (AFR) AF: 0.133 AC: 5538 AN: 41494

American (AMR) AF: 0.481 AC: 7356 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1873 AN: 3470

East Asian (EAS) AF: 0.483 AC: 2496 AN: 5168

South Asian (SAS) AF: 0.559 AC: 2697 AN: 4822

European-Finnish (FIN) AF: 0.510 AC: 5372 AN: 10530

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34204 AN: 67988

Other (OTH) AF: 0.415 AC: 877 AN: 2114

Alfa AF: 0.476 Hom.: 32853

Bravo AF: 0.382

Asia WGS AF: 0.452 AC: 1573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Benign	0.74
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3801148; hg19: chr7-139694500;