7-139953813-T-C

Variant names:

• chr7-139953813-T-C
• rs1003816
• NM_001061.7:c.539+357T>C

Variant summary

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

The NM_001166253.4(TBXAS1):​c.677+357T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,204 control chromosomes in the GnomAD database, including 56,907 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 0.86 (56907 hom., cov: 32)
• Consequence: TBXAS1 NM_001166253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173
• 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

ENSG00000305529 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166253.4. 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.539+357T>C		intron	N/A	NP_001052.3
	TBXAS1	NM_001166253.4		c.677+357T>C		intron	N/A	NP_001159725.2
	TBXAS1	NM_001130966.5		c.539+357T>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.539+357T>C		intron	N/A	ENSP00000402536.3
	TBXAS1	ENST00000336425.10	TSL:1	c.539+357T>C		intron	N/A	ENSP00000338087.7
	TBXAS1	ENST00000425687.5	TSL:1	c.338+357T>C		intron	N/A	ENSP00000388736.1

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131360 AN: 152086 Hom.: 56855 Cov.: 32

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.867

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

GnomAD4 genome AF: 0.864 AC: 131466 AN: 152204 Hom.: 56907 Cov.: 32 AF XY: 0.859 AC XY: 63915 AN XY: 74406

African (AFR) AF: 0.838 AC: 34777 AN: 41516

American (AMR) AF: 0.894 AC: 13679 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3029 AN: 3472

East Asian (EAS) AF: 0.750 AC: 3886 AN: 5182

South Asian (SAS) AF: 0.835 AC: 4033 AN: 4830

European-Finnish (FIN) AF: 0.794 AC: 8385 AN: 10560

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.893 AC: 60718 AN: 68024

Other (OTH) AF: 0.863 AC: 1824 AN: 2114

Alfa AF: 0.884 Hom.: 126473

Bravo AF: 0.869

Asia WGS AF: 0.792 AC: 2752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.0
DANN	Benign	0.64
PhyloP100		-0.17
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: rs1003816; hg19: chr7-139653612;