chr7-139810505-G-A

Variant names:

• chr7-139810505-G-A
• rs17178226
• ENST00000336425.10:c.-79-18807G>A

Variant summary

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

The ENST00000336425.10(TBXAS1):​c.-79-18807G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0946 in 152,170 control chromosomes in the GnomAD database, including 814 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 0.095 (814 hom., cov: 32)
• Consequence: TBXAS1 ENST00000336425.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.454
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000336425.10. 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_001130966.5		c.-79-18807G>A		intron	N/A	NP_001124438.2
	TBXAS1	NM_001166254.4		c.-113+23079G>A		intron	N/A	NP_001159726.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXAS1	ENST00000336425.10	TSL:1	c.-79-18807G>A		intron	N/A	ENSP00000338087.7
	TBXAS1	ENST00000425687.5	TSL:1	c.-113+23079G>A		intron	N/A	ENSP00000388736.1
	TBXAS1	ENST00000438104.6	TSL:5	c.-79-18807G>A		intron	N/A	ENSP00000388612.3

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14388 AN: 152052 Hom.: 813 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0665

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.0346

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.0880

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

GnomAD4 genome AF: 0.0946 AC: 14391 AN: 152170 Hom.: 814 Cov.: 32 AF XY: 0.0955 AC XY: 7105 AN XY: 74370

African (AFR) AF: 0.0363 AC: 1507 AN: 41514

American (AMR) AF: 0.0664 AC: 1015 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0911 AC: 316 AN: 3470

East Asian (EAS) AF: 0.0347 AC: 180 AN: 5184

South Asian (SAS) AF: 0.0479 AC: 231 AN: 4826

European-Finnish (FIN) AF: 0.187 AC: 1974 AN: 10568

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8905 AN: 67996

Other (OTH) AF: 0.0871 AC: 184 AN: 2112

Alfa AF: 0.114 Hom.: 383

Bravo AF: 0.0846

Asia WGS AF: 0.0400 AC: 138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.65
PhyloP100		0.45
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: rs17178226; hg19: chr7-139510304;