7-139941097-T-C

Variant names:

• chr7-139941097-T-C
• rs4726473
• NM_001061.7:c.450+4790T>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.450+4790T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,126 control chromosomes in the GnomAD database, including 44,163 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 0.76 (44163 hom., cov: 32)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• 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

LOC105375532 (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.787 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.450+4790T>C		intron	N/A	NP_001052.3
	TBXAS1	NM_001166253.4		c.450+4790T>C		intron	N/A	NP_001159725.2
	TBXAS1	NM_001130966.5		c.450+4790T>C		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.450+4790T>C		intron	N/A	ENSP00000402536.3
	TBXAS1	ENST00000336425.10	TSL:1	c.450+4790T>C		intron	N/A	ENSP00000338087.7
	TBXAS1	ENST00000425687.5	TSL:1	c.249+4790T>C		intron	N/A	ENSP00000388736.1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115756 AN: 152008 Hom.: 44134 Cov.: 32

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.761 AC: 115840 AN: 152126 Hom.: 44163 Cov.: 32 AF XY: 0.758 AC XY: 56377 AN XY: 74370

African (AFR) AF: 0.780 AC: 32359 AN: 41486

American (AMR) AF: 0.799 AC: 12223 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 2569 AN: 3468

East Asian (EAS) AF: 0.737 AC: 3809 AN: 5166

South Asian (SAS) AF: 0.738 AC: 3555 AN: 4818

European-Finnish (FIN) AF: 0.687 AC: 7261 AN: 10572

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.758 AC: 51550 AN: 68000

Other (OTH) AF: 0.762 AC: 1610 AN: 2112

Alfa AF: 0.760 Hom.: 72917

Bravo AF: 0.771

Asia WGS AF: 0.751 AC: 2612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.95
DANN	Benign	0.64
PhyloP100		-1.2
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: rs4726473; hg19: chr7-139640896;