NM_001061.7:c.89+16092T>G

Variant names:

• chr7-139845571-T-G
• rs2267682
• NM_001061.7:c.89+16092T>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.89+16092T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,928 control chromosomes in the GnomAD database, including 19,256 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 0.50 (19256 hom., cov: 31)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277
• 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 (SAS) allele frequency at 95% confidence interval = 0.675 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+16092T>G		intron	N/A	NP_001052.3
	TBXAS1	NM_001166253.4		c.89+16092T>G		intron	N/A	NP_001159725.2
	TBXAS1	NM_001130966.5		c.89+16092T>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.89+16092T>G		intron	N/A	ENSP00000402536.3
	TBXAS1	ENST00000336425.10	TSL:1	c.89+16092T>G		intron	N/A	ENSP00000338087.7
	TBXAS1	ENST00000425687.5	TSL:1	c.-112-26664T>G		intron	N/A	ENSP00000388736.1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 75993 AN: 151808 Hom.: 19243 Cov.: 31

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.501 AC: 76047 AN: 151928 Hom.: 19256 Cov.: 31 AF XY: 0.504 AC XY: 37444 AN XY: 74256

African (AFR) AF: 0.475 AC: 19673 AN: 41412

American (AMR) AF: 0.469 AC: 7149 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1819 AN: 3468

East Asian (EAS) AF: 0.687 AC: 3543 AN: 5160

South Asian (SAS) AF: 0.694 AC: 3346 AN: 4818

European-Finnish (FIN) AF: 0.509 AC: 5375 AN: 10566

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33395 AN: 67930

Other (OTH) AF: 0.516 AC: 1089 AN: 2112

Alfa AF: 0.496 Hom.: 22676

Bravo AF: 0.492

Asia WGS AF: 0.665 AC: 2315 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	1.6
DANN	Benign	0.71
PhyloP100		-0.28
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: rs2267682; hg19: chr7-139545370;