Genetic Variant TBXAS1:c.1134+4164T>C (chr7-139966397-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001061.7(TBXAS1):c.1134+4164T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,018 control chromosomes in the GnomAD database, including 47,269 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 0.79 ( 47269 hom., cov: 32)

Consequence

TBXAS1
NM_001061.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.95

Publications

4 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:

ENSG00000305529 (HGNC:):

ENSG00000305529 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXAS1	NM_001061.7 link	c.1134+4164T>C		intron_variant	Intron 9 of 12	ENST00000448866.7	NP_001052.3	P24557-1Q53F23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXAS1	ENST00000448866.7 link	c.1134+4164T>C		intron_variant	Intron 9 of 12	1	NM_001061.7	ENSP00000402536.3		P24557-1

Frequencies

GnomAD3 genomes

AF:

0.786

AC:

119323

AN:

151900

Hom.:

47249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.678

Gnomad AMI

AF:

0.932

Gnomad AMR

AF:

0.829

Gnomad ASJ

AF:

0.862

Gnomad EAS

AF:

0.878

Gnomad SAS

AF:

0.781

Gnomad FIN

AF:

0.762

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.832

Gnomad OTH

AF:

0.789

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

GnomAD4 genome

AF:

0.785

AC:

119372

AN:

152018

Hom.:

47269

Cov.:

AF XY:

0.782

AC XY:

58107

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.678

AC:

28026

AN:

41360

American (AMR)

AF:

0.830

AC:

12696

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.862

AC:

2990

AN:

3470

East Asian (EAS)

AF:

0.878

AC:

4547

AN:

5178

South Asian (SAS)

AF:

0.779

AC:

3759

AN:

4824

European-Finnish (FIN)

AF:

0.762

AC:

8055

AN:

10570

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.832

AC:

56559

AN:

67992

Other (OTH)

AF:

0.786

AC:

1664

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1281

2563

3844

5126

6407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

868

1736

2604

3472

4340

<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:

0.818

Hom.:

32222

Bravo

AF:

0.784

Asia WGS

AF:

0.789

AC:

2740

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.14

(source)

DANN

Benign

0.66

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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