7-139825825-G-T

Variant names:

• chr7-139825825-G-T
• rs1019178
• ENST00000336425.10:c.-79-3487G>T

Variant summary

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

The ENST00000336425.10(TBXAS1):​c.-79-3487G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,052 control chromosomes in the GnomAD database, including 20,336 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 0.50 (20336 hom., cov: 32)
• Consequence: TBXAS1 ENST00000336425.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293
• 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: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000336425.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXAS1	NM_001130966.5		c.-79-3487G>T		intron	N/A	NP_001124438.2
	TBXAS1	NM_001166254.4		c.-113+38399G>T		intron	N/A	NP_001159726.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXAS1	ENST00000336425.10	TSL:1	c.-79-3487G>T		intron	N/A	ENSP00000338087.7
	TBXAS1	ENST00000425687.5	TSL:1	c.-113+38399G>T		intron	N/A	ENSP00000388736.1
	TBXAS1	ENST00000438104.6	TSL:5	c.-79-3487G>T		intron	N/A	ENSP00000388612.3

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76520 AN: 151934 Hom.: 20307 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.504 AC: 76603 AN: 152052 Hom.: 20336 Cov.: 32 AF XY: 0.508 AC XY: 37720 AN XY: 74324

African (AFR) AF: 0.555 AC: 23008 AN: 41462

American (AMR) AF: 0.601 AC: 9188 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1626 AN: 3472

East Asian (EAS) AF: 0.880 AC: 4562 AN: 5182

South Asian (SAS) AF: 0.717 AC: 3450 AN: 4814

European-Finnish (FIN) AF: 0.363 AC: 3830 AN: 10552

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29308 AN: 67976

Other (OTH) AF: 0.526 AC: 1109 AN: 2108

Alfa AF: 0.476 Hom.: 14508

Bravo AF: 0.524

Asia WGS AF: 0.777 AC: 2704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.75
PhyloP100		0.29
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: rs1019178; hg19: chr7-139525624;