NM_001061.7:c.333+6881T>A

Variant names:

• chr7-139918202-T-A
• rs2299891
• NM_001061.7:c.333+6881T>A

Variant summary

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

The NM_001061.7(TBXAS1):​c.333+6881T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,042 control chromosomes in the GnomAD database, including 26,612 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 0.57 (26612 hom., cov: 31)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.662 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.333+6881T>A		intron	N/A	NP_001052.3
	TBXAS1	NM_001166253.4		c.333+6881T>A		intron	N/A	NP_001159725.2
	TBXAS1	NM_001130966.5		c.333+6881T>A		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.333+6881T>A		intron	N/A	ENSP00000402536.3
	TBXAS1	ENST00000336425.10	TSL:1	c.333+6881T>A		intron	N/A	ENSP00000338087.7
	TBXAS1	ENST00000425687.5	TSL:1	c.132+6881T>A		intron	N/A	ENSP00000388736.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87118 AN: 151924 Hom.: 26611 Cov.: 31

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.573 AC: 87131 AN: 152042 Hom.: 26612 Cov.: 31 AF XY: 0.577 AC XY: 42865 AN XY: 74314

African (AFR) AF: 0.344 AC: 14282 AN: 41458

American (AMR) AF: 0.621 AC: 9480 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2276 AN: 3468

East Asian (EAS) AF: 0.671 AC: 3467 AN: 5168

South Asian (SAS) AF: 0.516 AC: 2484 AN: 4818

European-Finnish (FIN) AF: 0.720 AC: 7618 AN: 10574

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.667 AC: 45337 AN: 67970

Other (OTH) AF: 0.593 AC: 1253 AN: 2114

Alfa AF: 0.603 Hom.: 3579

Bravo AF: 0.559

Asia WGS AF: 0.562 AC: 1951 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.40
PhyloP100		-0.29
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: rs2299891; hg19: chr7-139618001;