7-139828863-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000336425.10(TBXAS1):c.-79-449G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,128 control chromosomes in the GnomAD database, including 37,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (37347 hom., cov: 32)
• Consequence: TBXAS1 ENST00000336425.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.427

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 7-139828863-G-T is Benign according to our data. Variant chr7-139828863-G-T is described in ClinVar as [Benign]. Clinvar id is 1227899.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBXAS1	NM_001130966.5	c.-79-449G>T		intron_variant
TBXAS1	NM_001166254.4	c.-113+41437G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBXAS1	ENST00000336425.10	c.-79-449G>T		intron_variant		1		P1
TBXAS1	ENST00000425687.5	c.-113+41437G>T		intron_variant		1
TBXAS1	ENST00000438104.6	c.-79-449G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103733 AN: 152010 Hom.: 37282 Cov.: 32

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.683 AC: 103859 AN: 152128 Hom.: 37347 Cov.: 32 AF XY: 0.685 AC XY: 50958 AN XY: 74358

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.922

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.668

Alfa AF: 0.584 Hom.: 26006

Bravo AF: 0.704

Asia WGS AF: 0.839 AC: 2917 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.1
Dann	Benign	0.72

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: rs4590360; hg19: chr7-139528662;