rs8192813

Variant names:

• chr7-139879378-C-T
• rs8192813
• NM_001061.7:c.236+3741C>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.236+3741C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0622 in 152,078 control chromosomes in the GnomAD database, including 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 0.062 (401 hom., cov: 32)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.116 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.236+3741C>T		intron	N/A	NP_001052.3	P24557-1
	TBXAS1	NM_001166253.4		c.236+3741C>T		intron	N/A	NP_001159725.2	P24557-3
	TBXAS1	NM_001130966.5		c.236+3741C>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.236+3741C>T		intron	N/A	ENSP00000402536.3	P24557-1
	TBXAS1	ENST00000336425.10	TSL:1	c.236+3741C>T		intron	N/A	ENSP00000338087.7	P24557-1
	TBXAS1	ENST00000425687.5	TSL:1	c.35+3741C>T		intron	N/A	ENSP00000388736.1	P24557-2

Frequencies

GnomAD3 genomes AF: 0.0621 AC: 9440 AN: 151960 Hom.: 394 Cov.: 32

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0649

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.0557

Gnomad FIN AF: 0.0715

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0497

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0622 AC: 9458 AN: 152078 Hom.: 401 Cov.: 32 AF XY: 0.0653 AC XY: 4851 AN XY: 74328

African (AFR) AF: 0.0520 AC: 2158 AN: 41494

American (AMR) AF: 0.118 AC: 1792 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0649 AC: 225 AN: 3466

East Asian (EAS) AF: 0.124 AC: 639 AN: 5168

South Asian (SAS) AF: 0.0561 AC: 270 AN: 4810

European-Finnish (FIN) AF: 0.0715 AC: 756 AN: 10568

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0497 AC: 3380 AN: 68006

Other (OTH) AF: 0.0478 AC: 101 AN: 2112

Alfa AF: 0.0540 Hom.: 451

Bravo AF: 0.0650

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.1
DANN	Benign	0.24
PhyloP100		1.1
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: rs8192813; hg19: chr7-139579177;