Genetic Variant ENST00000336425.10:c.-79-3899G>A (chr7-139825413-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000336425.10(TBXAS1):c.-79-3899G>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 152,204 control chromosomes in the GnomAD database, including 929 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 ( 929 hom., cov: 32)

Consequence

TBXAS1
ENST00000336425.10 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14

Publications

5 publications found

Variant links:

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

TBXAS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXAS1	NM_001130966.5 link	c.-79-3899G>A		intron_variant	Intron 4 of 16		NP_001124438.2
TBXAS1	NM_001166254.4 link	c.-113+37987G>A		intron_variant	Intron 3 of 14		NP_001159726.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
TBXAS1	ENST00000336425.10 link	c.-79-3899G>A	intron_variant	Intron 4 of 16	1	ENSP00000338087.7
TBXAS1	ENST00000425687.5 link	c.-113+37987G>A	intron_variant	Intron 3 of 14	1	ENSP00000388736.1
TBXAS1	ENST00000438104.6 link	c.-79-3899G>A	intron_variant	Intron 2 of 6	5	ENSP00000388612.3

Frequencies

GnomAD3 genomes

AF:

0.0948

AC:

14419

AN:

152086

Hom.:

929

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0237

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0657

Gnomad ASJ

AF:

0.0378

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0287

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.0801

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

GnomAD4 genome

AF:

0.0946

AC:

14406

AN:

152204

Hom.:

929

Cov.:

AF XY:

0.0913

AC XY:

6791

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0236

AC:

980

AN:

41554

American (AMR)

AF:

0.0656

AC:

1003

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0378

AC:

131

AN:

3470

East Asian (EAS)

AF:

0.110

AC:

569

AN:

5182

South Asian (SAS)

AF:

0.118

AC:

568

AN:

4812

European-Finnish (FIN)

AF:

0.105

AC:

1111

AN:

10590

Middle Eastern (MID)

AF:

0.0308

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.144

AC:

9824

AN:

67990

Other (OTH)

AF:

0.0783

AC:

165

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

664

1328

1993

2657

3321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.124

Hom.:

2765

Bravo

AF:

0.0873

Asia WGS

AF:

0.130

AC:

454

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over