rs17161326

Variant names:

• chr7-139993371-T-A
• rs17161326
• NM_001061.7:c.1135-13720T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-139993371-T-A
• chr7-139993371-T-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.1135-13720T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,074 control chromosomes in the GnomAD database, including 3,917 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 0.21 (3917 hom., cov: 32)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXAS1	NM_001061.7	c.1135-13720T>A		intron_variant	Intron 9 of 12	ENST00000448866.7	NP_001052.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXAS1	ENST00000448866.7	c.1135-13720T>A		intron_variant	Intron 9 of 12	1	NM_001061.7	ENSP00000402536.3

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31529 AN: 151954 Hom.: 3908 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0901

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.208 AC: 31581 AN: 152074 Hom.: 3917 Cov.: 32 AF XY: 0.206 AC XY: 15342 AN XY: 74356

African (AFR) AF: 0.350 AC: 14490 AN: 41414

American (AMR) AF: 0.240 AC: 3664 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3472

East Asian (EAS) AF: 0.0901 AC: 467 AN: 5186

South Asian (SAS) AF: 0.109 AC: 527 AN: 4822

European-Finnish (FIN) AF: 0.139 AC: 1471 AN: 10582

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10027 AN: 67996

Other (OTH) AF: 0.196 AC: 413 AN: 2106

Alfa AF: 0.0849 Hom.: 121

Bravo AF: 0.226

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.84
DANN	Benign	0.75
PhyloP100		-2.7
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: rs17161326; hg19: chr7-139693170; COSMIC: COSV54954595;