7-139984244-T-G

Variant names:

• chr7-139984244-T-G
• rs10487667
• NM_001061.7:c.1134+22011T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001061.7(TBXAS1):​c.1134+22011T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,938 control chromosomes in the GnomAD database, including 5,459 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 0.26 (5459 hom., cov: 32)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.397 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.1134+22011T>G		intron	N/A	NP_001052.3
	TBXAS1	NM_001166253.4		c.1272+22011T>G		intron	N/A	NP_001159725.2
	TBXAS1	NM_001130966.5		c.1134+22011T>G		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.1134+22011T>G		intron	N/A	ENSP00000402536.3
	TBXAS1	ENST00000336425.10	TSL:1	c.1134+22011T>G		intron	N/A	ENSP00000338087.7
	TBXAS1	ENST00000425687.5	TSL:1	c.933+22011T>G		intron	N/A	ENSP00000388736.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40053 AN: 151820 Hom.: 5459 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.264 AC: 40054 AN: 151938 Hom.: 5459 Cov.: 32 AF XY: 0.268 AC XY: 19884 AN XY: 74250

African (AFR) AF: 0.214 AC: 8875 AN: 41396

American (AMR) AF: 0.310 AC: 4726 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1227 AN: 3468

East Asian (EAS) AF: 0.316 AC: 1630 AN: 5154

South Asian (SAS) AF: 0.413 AC: 1983 AN: 4806

European-Finnish (FIN) AF: 0.242 AC: 2557 AN: 10568

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 17982 AN: 67984

Other (OTH) AF: 0.287 AC: 606 AN: 2110

Alfa AF: 0.265 Hom.: 10688

Bravo AF: 0.263

Asia WGS AF: 0.321 AC: 1117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.59
PhyloP100		-0.40
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: rs10487667; hg19: chr7-139684043;