rs4725563

Variant names:

• chr7-139954457-C-T
• rs4725563
• NM_001061.7:c.539+1001C>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.539+1001C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 152,146 control chromosomes in the GnomAD database, including 42,842 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 0.75 (42842 hom., cov: 32)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.844
• 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

ENSG00000305529 (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXAS1	NM_001061.7	c.539+1001C>T		intron_variant	Intron 6 of 12	ENST00000448866.7	NP_001052.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXAS1	ENST00000448866.7	c.539+1001C>T		intron_variant	Intron 6 of 12	1	NM_001061.7	ENSP00000402536.3

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113771 AN: 152028 Hom.: 42807 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.748 AC: 113852 AN: 152146 Hom.: 42842 Cov.: 32 AF XY: 0.744 AC XY: 55334 AN XY: 74368

African (AFR) AF: 0.698 AC: 28967 AN: 41492

American (AMR) AF: 0.811 AC: 12405 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2633 AN: 3472

East Asian (EAS) AF: 0.745 AC: 3859 AN: 5182

South Asian (SAS) AF: 0.727 AC: 3499 AN: 4816

European-Finnish (FIN) AF: 0.666 AC: 7033 AN: 10562

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52846 AN: 68006

Other (OTH) AF: 0.741 AC: 1564 AN: 2112

Alfa AF: 0.768 Hom.: 36492

Bravo AF: 0.756

Asia WGS AF: 0.733 AC: 2544 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.26
DANN	Benign	0.76
PhyloP100		-0.84
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: rs4725563; hg19: chr7-139654256;