7-139991120-A-T

Variant names:

• chr7-139991120-A-T
• rs8192856
• NM_001061.7:c.1135-15971A>T

Variant summary

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

The NM_001061.7(TBXAS1):​c.1135-15971A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 152,310 control chromosomes in the GnomAD database, including 408 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 0.064 (408 hom., cov: 31)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 4 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: G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001061.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXAS1	NM_001061.7	MANE Select	c.1135-15971A>T		intron	N/A	NP_001052.3	P24557-1
	TBXAS1	NM_001166253.4		c.1273-15971A>T		intron	N/A	NP_001159725.2	P24557-3
	TBXAS1	NM_001130966.5		c.1135-15971A>T		intron	N/A	NP_001124438.2	P24557-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXAS1	ENST00000448866.7	TSL:1 MANE Select	c.1135-15971A>T		intron	N/A	ENSP00000402536.3	P24557-1
	TBXAS1	ENST00000336425.10	TSL:1	c.1135-15971A>T		intron	N/A	ENSP00000338087.7	P24557-1
	TBXAS1	ENST00000425687.5	TSL:1	c.934-15971A>T		intron	N/A	ENSP00000388736.1	P24557-2

Frequencies

GnomAD3 genomes AF: 0.0637 AC: 9690 AN: 152192 Hom.: 408 Cov.: 31

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0579

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.0670

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0753

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.0852

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

GnomAD4 genome AF: 0.0636 AC: 9686 AN: 152310 Hom.: 408 Cov.: 31 AF XY: 0.0634 AC XY: 4723 AN XY: 74470

African (AFR) AF: 0.0173 AC: 721 AN: 41568

American (AMR) AF: 0.0578 AC: 885 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3468

East Asian (EAS) AF: 0.0672 AC: 348 AN: 5182

South Asian (SAS) AF: 0.119 AC: 576 AN: 4828

European-Finnish (FIN) AF: 0.0753 AC: 799 AN: 10614

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0852 AC: 5799 AN: 68026

Other (OTH) AF: 0.0838 AC: 177 AN: 2112

Alfa AF: 0.0414 Hom.: 33

Bravo AF: 0.0578

Asia WGS AF: 0.0730 AC: 255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.10
DANN	Benign	0.77
PhyloP100		-1.2
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: rs8192856; hg19: chr7-139690919;