7-139839419-C-T

Variant names:

• chr7-139839419-C-T
• rs2267679
• NM_001061.7:c.89+9940C>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.89+9940C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 151,968 control chromosomes in the GnomAD database, including 37,518 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 0.69 (37518 hom., cov: 30)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.804
• 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

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 (EAS) allele frequency at 95% confidence interval = 0.9 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXAS1	NM_001061.7	MANE Select	c.89+9940C>T		intron	N/A	NP_001052.3
	TBXAS1	NM_001166253.4		c.89+9940C>T		intron	N/A	NP_001159725.2
	TBXAS1	NM_001130966.5		c.89+9940C>T		intron	N/A	NP_001124438.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXAS1	ENST00000448866.7	TSL:1 MANE Select	c.89+9940C>T		intron	N/A	ENSP00000402536.3
	TBXAS1	ENST00000336425.10	TSL:1	c.89+9940C>T		intron	N/A	ENSP00000338087.7
	TBXAS1	ENST00000425687.5	TSL:1	c.-112-32816C>T		intron	N/A	ENSP00000388736.1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104005 AN: 151850 Hom.: 37453 Cov.: 30

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.685 AC: 104131 AN: 151968 Hom.: 37518 Cov.: 30 AF XY: 0.688 AC XY: 51088 AN XY: 74282

African (AFR) AF: 0.898 AC: 37223 AN: 41464

American (AMR) AF: 0.695 AC: 10617 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2055 AN: 3472

East Asian (EAS) AF: 0.922 AC: 4769 AN: 5174

South Asian (SAS) AF: 0.766 AC: 3681 AN: 4804

European-Finnish (FIN) AF: 0.550 AC: 5788 AN: 10528

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37878 AN: 67934

Other (OTH) AF: 0.673 AC: 1417 AN: 2106

Alfa AF: 0.594 Hom.: 44968

Bravo AF: 0.706

Asia WGS AF: 0.838 AC: 2915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.38
PhyloP100		-0.80
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: rs2267679; hg19: chr7-139539218;