rs10277664

Variant names:

• chr7-139806781-C-T
• rs10277664
• ENST00000336425.10:c.-80+19355C>T

Variant summary

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

The ENST00000336425.10(TBXAS1):​c.-80+19355C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,880 control chromosomes in the GnomAD database, including 11,027 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 0.36 (11027 hom., cov: 31)
• Consequence: TBXAS1 ENST00000336425.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000336425.10. 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_001130966.5		c.-80+19355C>T		intron	N/A	NP_001124438.2
	TBXAS1	NM_001166254.4		c.-113+19355C>T		intron	N/A	NP_001159726.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXAS1	ENST00000336425.10	TSL:1	c.-80+19355C>T		intron	N/A	ENSP00000338087.7
	TBXAS1	ENST00000425687.5	TSL:1	c.-113+19355C>T		intron	N/A	ENSP00000388736.1
	TBXAS1	ENST00000438104.6	TSL:5	c.-80+19355C>T		intron	N/A	ENSP00000388612.3

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55276 AN: 151762 Hom.: 11031 Cov.: 31

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.364 AC: 55283 AN: 151880 Hom.: 11027 Cov.: 31 AF XY: 0.367 AC XY: 27244 AN XY: 74256

African (AFR) AF: 0.229 AC: 9483 AN: 41418

American (AMR) AF: 0.397 AC: 6054 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1428 AN: 3470

East Asian (EAS) AF: 0.567 AC: 2921 AN: 5148

South Asian (SAS) AF: 0.665 AC: 3204 AN: 4816

European-Finnish (FIN) AF: 0.320 AC: 3378 AN: 10560

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27506 AN: 67900

Other (OTH) AF: 0.385 AC: 811 AN: 2108

Alfa AF: 0.410 Hom.: 9090

Bravo AF: 0.358

Asia WGS AF: 0.582 AC: 2021 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.31
DANN	Benign	0.51
PhyloP100		-2.9
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: rs10277664; hg19: chr7-139506580;