NM_001061.7:c.1134+9085T>A

Variant names:

• chr7-139971318-T-A
• rs6962291
• NM_001061.7:c.1134+9085T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001061.7(TBXAS1):​c.1134+9085T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,856 control chromosomes in the GnomAD database, including 10,049 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 0.36 (10049 hom., cov: 31)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 23 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

ENSG00000305529 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXAS1	NM_001061.7	c.1134+9085T>A		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.1134+9085T>A		intron_variant	Intron 9 of 12	1	NM_001061.7	ENSP00000402536.3

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54505 AN: 151736 Hom.: 10041 Cov.: 31

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.359 AC: 54539 AN: 151856 Hom.: 10049 Cov.: 31 AF XY: 0.361 AC XY: 26804 AN XY: 74222

African (AFR) AF: 0.384 AC: 15885 AN: 41380

American (AMR) AF: 0.427 AC: 6523 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1153 AN: 3466

East Asian (EAS) AF: 0.500 AC: 2574 AN: 5152

South Asian (SAS) AF: 0.408 AC: 1966 AN: 4816

European-Finnish (FIN) AF: 0.311 AC: 3275 AN: 10542

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.323 AC: 21910 AN: 67914

Other (OTH) AF: 0.388 AC: 822 AN: 2116

Alfa AF: 0.337 Hom.: 1326

Bravo AF: 0.368

Asia WGS AF: 0.417 AC: 1450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.30
DANN	Benign	0.67
PhyloP100		-2.4
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: rs6962291; hg19: chr7-139671117;