7-139970695-G-T

Variant names:

• chr7-139970695-G-T
• rs42334
• NM_001061.7:c.1134+8462G>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.1134+8462G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 152,214 control chromosomes in the GnomAD database, including 54,370 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 0.84 (54370 hom., cov: 33)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.776
• 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: 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.881 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXAS1	NM_001061.7	MANE Select	c.1134+8462G>T		intron	N/A	NP_001052.3
	TBXAS1	NM_001166253.4		c.1272+8462G>T		intron	N/A	NP_001159725.2
	TBXAS1	NM_001130966.5		c.1134+8462G>T		intron	N/A	NP_001124438.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXAS1	ENST00000448866.7	TSL:1 MANE Select	c.1134+8462G>T		intron	N/A	ENSP00000402536.3
	TBXAS1	ENST00000336425.10	TSL:1	c.1134+8462G>T		intron	N/A	ENSP00000338087.7
	TBXAS1	ENST00000425687.5	TSL:1	c.933+8462G>T		intron	N/A	ENSP00000388736.1

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128351 AN: 152096 Hom.: 54362 Cov.: 33

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.941

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.843 AC: 128387 AN: 152214 Hom.: 54370 Cov.: 33 AF XY: 0.840 AC XY: 62541 AN XY: 74440

African (AFR) AF: 0.765 AC: 31745 AN: 41500

American (AMR) AF: 0.865 AC: 13234 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 2998 AN: 3468

East Asian (EAS) AF: 0.858 AC: 4449 AN: 5184

South Asian (SAS) AF: 0.795 AC: 3838 AN: 4828

European-Finnish (FIN) AF: 0.836 AC: 8860 AN: 10602

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60350 AN: 68012

Other (OTH) AF: 0.853 AC: 1804 AN: 2114

Alfa AF: 0.870 Hom.: 109032

Bravo AF: 0.843

Asia WGS AF: 0.791 AC: 2747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.76
DANN	Benign	0.50
PhyloP100		-0.78
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: rs42334; hg19: chr7-139670494;