chr7-139853291-C-T

Variant names:

• chr7-139853291-C-T
• rs12532529
• NM_001061.7:c.90-18944C>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.90-18944C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,056 control chromosomes in the GnomAD database, including 4,499 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 0.21 (4499 hom., cov: 32)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.956
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXAS1	NM_001061.7	c.90-18944C>T		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.90-18944C>T		intron_variant	Intron 1 of 12	1	NM_001061.7	ENSP00000402536.3

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31774 AN: 151938 Hom.: 4476 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0804

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.209 AC: 31843 AN: 152056 Hom.: 4499 Cov.: 32 AF XY: 0.208 AC XY: 15468 AN XY: 74348

African (AFR) AF: 0.402 AC: 16645 AN: 41424

American (AMR) AF: 0.201 AC: 3067 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 420 AN: 3470

East Asian (EAS) AF: 0.153 AC: 793 AN: 5182

South Asian (SAS) AF: 0.0800 AC: 386 AN: 4824

European-Finnish (FIN) AF: 0.162 AC: 1712 AN: 10576

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8233 AN: 67986

Other (OTH) AF: 0.191 AC: 403 AN: 2108

Alfa AF: 0.140 Hom.: 3730

Bravo AF: 0.225

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.38
DANN	Benign	0.47
PhyloP100		-0.96
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: rs12532529; hg19: chr7-139553090;