rs4726460

Variant names:

• chr7-139924674-G-A
• rs4726460
• NM_001061.7:c.334-11517G>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.334-11517G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,926 control chromosomes in the GnomAD database, including 13,957 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 0.40 (13957 hom., cov: 31)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.498 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.334-11517G>A		intron	N/A	NP_001052.3	P24557-1
	TBXAS1	NM_001166253.4		c.334-11517G>A		intron	N/A	NP_001159725.2	P24557-3
	TBXAS1	NM_001130966.5		c.334-11517G>A		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.334-11517G>A		intron	N/A	ENSP00000402536.3	P24557-1
	TBXAS1	ENST00000336425.10	TSL:1	c.334-11517G>A		intron	N/A	ENSP00000338087.7	P24557-1
	TBXAS1	ENST00000425687.5	TSL:1	c.133-11517G>A		intron	N/A	ENSP00000388736.1	P24557-2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60654 AN: 151806 Hom.: 13951 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.399 AC: 60671 AN: 151926 Hom.: 13957 Cov.: 31 AF XY: 0.404 AC XY: 30002 AN XY: 74250

African (AFR) AF: 0.161 AC: 6650 AN: 41424

American (AMR) AF: 0.459 AC: 7005 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1530 AN: 3472

East Asian (EAS) AF: 0.436 AC: 2248 AN: 5160

South Asian (SAS) AF: 0.305 AC: 1465 AN: 4808

European-Finnish (FIN) AF: 0.587 AC: 6188 AN: 10540

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34156 AN: 67940

Other (OTH) AF: 0.396 AC: 836 AN: 2110

Alfa AF: 0.434 Hom.: 2041

Bravo AF: 0.381

Asia WGS AF: 0.354 AC: 1229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.48
PhyloP100		-0.65
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: rs4726460; hg19: chr7-139624473;