7-139830129-G-C

Variant names:

• chr7-139830129-G-C
• rs764745
• NM_001061.7:c.89+650G>C

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+650G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,008 control chromosomes in the GnomAD database, including 37,317 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 0.68 (37317 hom., cov: 31)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456
• Publications: 1 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=-0.73).
• 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+650G>C		intron	N/A	NP_001052.3
	TBXAS1	NM_001166253.4		c.89+650G>C		intron	N/A	NP_001159725.2
	TBXAS1	NM_001130966.5		c.89+650G>C		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+650G>C		intron	N/A	ENSP00000402536.3
	TBXAS1	ENST00000336425.10	TSL:1	c.89+650G>C		intron	N/A	ENSP00000338087.7
	TBXAS1	ENST00000425687.5	TSL:1	c.-112-42106G>C		intron	N/A	ENSP00000388736.1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103656 AN: 151890 Hom.: 37252 Cov.: 31

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.683 AC: 103782 AN: 152008 Hom.: 37317 Cov.: 31 AF XY: 0.685 AC XY: 50920 AN XY: 74284

African (AFR) AF: 0.897 AC: 37187 AN: 41462

American (AMR) AF: 0.693 AC: 10590 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1911 AN: 3464

East Asian (EAS) AF: 0.922 AC: 4772 AN: 5174

South Asian (SAS) AF: 0.767 AC: 3703 AN: 4826

European-Finnish (FIN) AF: 0.549 AC: 5786 AN: 10544

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37715 AN: 67938

Other (OTH) AF: 0.670 AC: 1414 AN: 2110

Alfa AF: 0.485 Hom.: 1237

Bravo AF: 0.704

Asia WGS AF: 0.839 AC: 2917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	10
DANN	Benign	0.74
PhyloP100		-0.46
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: rs764745; hg19: chr7-139529928;