7-139810505-G-A

Position:

• chr7-139810505-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBXAS1	NM_001130966.5	c.-79-18807G>A		intron_variant			NP_001124438.2
TBXAS1	NM_001166254.4	c.-113+23079G>A		intron_variant			NP_001159726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBXAS1	ENST00000336425.10	c.-79-18807G>A		intron_variant		1		ENSP00000338087	P1
TBXAS1	ENST00000425687.5	c.-113+23079G>A		intron_variant		1		ENSP00000388736
TBXAS1	ENST00000438104.6	c.-79-18807G>A		intron_variant		5		ENSP00000388612

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

Gnomad4 AFR AF: 0.0363

Gnomad4 AMR AF: 0.0664

Gnomad4 ASJ AF: 0.0911

Gnomad4 EAS AF: 0.0347

Gnomad4 SAS AF: 0.0479

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.0871

Alfa AF: 0.118 Hom.: 241

Bravo AF: 0.0846

Asia WGS AF: 0.0400 AC: 138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs17178226; hg19: chr7-139510304;