7-139943319-C-T

Variant names:

• chr7-139943319-C-T
• rs13239058
• NM_001061.7:c.450+7012C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001061.7(TBXAS1):​c.450+7012C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,164 control chromosomes in the GnomAD database, including 1,963 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 0.14 (1963 hom., cov: 33)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.936
• 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

LOC105375532 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXAS1	NM_001061.7	c.450+7012C>T		intron_variant	Intron 5 of 12	ENST00000448866.7	NP_001052.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXAS1	ENST00000448866.7	c.450+7012C>T		intron_variant	Intron 5 of 12	1	NM_001061.7	ENSP00000402536.3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21861 AN: 152046 Hom.: 1962 Cov.: 33

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0776

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.144 AC: 21861 AN: 152164 Hom.: 1963 Cov.: 33 AF XY: 0.143 AC XY: 10617 AN XY: 74372

African (AFR) AF: 0.0421 AC: 1747 AN: 41538

American (AMR) AF: 0.182 AC: 2778 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 497 AN: 3466

East Asian (EAS) AF: 0.0775 AC: 402 AN: 5184

South Asian (SAS) AF: 0.110 AC: 530 AN: 4812

European-Finnish (FIN) AF: 0.182 AC: 1926 AN: 10578

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13537 AN: 67980

Other (OTH) AF: 0.143 AC: 303 AN: 2112

Alfa AF: 0.180 Hom.: 2036

Bravo AF: 0.139

Asia WGS AF: 0.0970 AC: 338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.67
PhyloP100		0.94
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: rs13239058; hg19: chr7-139643118;