chr7-139858487-T-A

Variant names:

• chr7-139858487-T-A
• rs194150
• NM_001061.7:c.90-13748T>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.90-13748T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 152,068 control chromosomes in the GnomAD database, including 29,495 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 0.61 (29495 hom., cov: 32)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• 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

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 = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXAS1	NM_001061.7	c.90-13748T>A		intron_variant	Intron 1 of 12	ENST00000448866.7	NP_001052.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXAS1	ENST00000448866.7	c.90-13748T>A		intron_variant	Intron 1 of 12	1	NM_001061.7	ENSP00000402536.3

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92831 AN: 151950 Hom.: 29500 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.610 AC: 92836 AN: 152068 Hom.: 29495 Cov.: 32 AF XY: 0.611 AC XY: 45408 AN XY: 74328

African (AFR) AF: 0.431 AC: 17882 AN: 41444

American (AMR) AF: 0.646 AC: 9865 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2199 AN: 3470

East Asian (EAS) AF: 0.582 AC: 3008 AN: 5166

South Asian (SAS) AF: 0.443 AC: 2133 AN: 4818

European-Finnish (FIN) AF: 0.740 AC: 7841 AN: 10592

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47775 AN: 67984

Other (OTH) AF: 0.616 AC: 1299 AN: 2110

Alfa AF: 0.676 Hom.: 19478

Bravo AF: 0.604

Asia WGS AF: 0.477 AC: 1655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.31
PhyloP100		0.10
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: rs194150; hg19: chr7-139558286;