chr7-139858148-C-T

Variant names:

• chr7-139858148-C-T
• rs194151
• NM_001061.7:c.90-14087C>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.90-14087C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,050 control chromosomes in the GnomAD database, including 16,972 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 0.45 (16972 hom., cov: 31)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXAS1	NM_001061.7	c.90-14087C>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.90-14087C>T		intron_variant	Intron 1 of 12	1	NM_001061.7	ENSP00000402536.3

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67807 AN: 151932 Hom.: 16976 Cov.: 31

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.446 AC: 67799 AN: 152050 Hom.: 16972 Cov.: 31 AF XY: 0.447 AC XY: 33203 AN XY: 74314

African (AFR) AF: 0.207 AC: 8606 AN: 41484

American (AMR) AF: 0.454 AC: 6943 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1748 AN: 3468

East Asian (EAS) AF: 0.519 AC: 2680 AN: 5168

South Asian (SAS) AF: 0.380 AC: 1832 AN: 4818

European-Finnish (FIN) AF: 0.570 AC: 6027 AN: 10570

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38357 AN: 67938

Other (OTH) AF: 0.471 AC: 994 AN: 2112

Alfa AF: 0.480 Hom.: 17422

Bravo AF: 0.430

Asia WGS AF: 0.403 AC: 1399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.085
DANN	Benign	0.66
PhyloP100		-0.59
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: rs194151; hg19: chr7-139557947;