rs3801153

Variant names:

• chr7-139888377-T-C
• rs3801153
• NM_001061.7:c.236+12740T>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.236+12740T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,178 control chromosomes in the GnomAD database, including 1,281 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 0.12 (1281 hom., cov: 32)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.788
• 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: G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen

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 (AMR) allele frequency at 95% confidence interval = 0.182 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXAS1	NM_001061.7	MANE Select	c.236+12740T>C		intron	N/A	NP_001052.3	P24557-1
	TBXAS1	NM_001166253.4		c.236+12740T>C		intron	N/A	NP_001159725.2	P24557-3
	TBXAS1	NM_001130966.5		c.236+12740T>C		intron	N/A	NP_001124438.2	P24557-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXAS1	ENST00000448866.7	TSL:1 MANE Select	c.236+12740T>C		intron	N/A	ENSP00000402536.3	P24557-1
	TBXAS1	ENST00000336425.10	TSL:1	c.236+12740T>C		intron	N/A	ENSP00000338087.7	P24557-1
	TBXAS1	ENST00000425687.5	TSL:1	c.35+12740T>C		intron	N/A	ENSP00000388736.1	P24557-2

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18804 AN: 152060 Hom.: 1281 Cov.: 32

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0679

Gnomad SAS AF: 0.0670

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.124 AC: 18804 AN: 152178 Hom.: 1281 Cov.: 32 AF XY: 0.125 AC XY: 9292 AN XY: 74420

African (AFR) AF: 0.0858 AC: 3562 AN: 41520

American (AMR) AF: 0.188 AC: 2867 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3464

East Asian (EAS) AF: 0.0681 AC: 353 AN: 5184

South Asian (SAS) AF: 0.0668 AC: 323 AN: 4832

European-Finnish (FIN) AF: 0.160 AC: 1700 AN: 10606

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9065 AN: 67982

Other (OTH) AF: 0.123 AC: 259 AN: 2110

Alfa AF: 0.130 Hom.: 2290

Bravo AF: 0.127

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.71
DANN	Benign	0.47
PhyloP100		-0.79
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: rs3801153; hg19: chr7-139588176;