rs4726499

Variant names:

• chr7-139988205-G-A
• rs4726499
• NM_001061.7:c.1135-18886G>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.1135-18886G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,240 control chromosomes in the GnomAD database, including 51,659 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 0.82 (51659 hom., cov: 33)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXAS1	NM_001061.7	c.1135-18886G>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.1135-18886G>A		intron_variant	Intron 9 of 12	1	NM_001061.7	ENSP00000402536.3

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124875 AN: 152122 Hom.: 51592 Cov.: 33

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.843

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

GnomAD4 genome AF: 0.821 AC: 125001 AN: 152240 Hom.: 51659 Cov.: 33 AF XY: 0.822 AC XY: 61182 AN XY: 74432

African (AFR) AF: 0.887 AC: 36863 AN: 41548

American (AMR) AF: 0.864 AC: 13220 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2946 AN: 3470

East Asian (EAS) AF: 0.989 AC: 5121 AN: 5176

South Asian (SAS) AF: 0.826 AC: 3988 AN: 4830

European-Finnish (FIN) AF: 0.717 AC: 7591 AN: 10592

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.774 AC: 52608 AN: 68000

Other (OTH) AF: 0.844 AC: 1784 AN: 2114

Alfa AF: 0.792 Hom.: 83596

Bravo AF: 0.835

Asia WGS AF: 0.919 AC: 3193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.72
PhyloP100		0.24
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: rs4726499; hg19: chr7-139688004;