rs1131882

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000589966.1(TBXA2R):c.406C>T(p.Arg136Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,590,290 control chromosomes in the GnomAD database, including 29,341 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R136S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.16 ( 2815 hom., cov: 32)

Exomes 𝑓: 0.17 ( 26526 hom. )

Consequence

TBXA2R
ENST00000589966.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.249

Publications

63 publications found

Variant links:

Genes affected

TBXA2R (HGNC:11608): (thromboxane A2 receptor) This gene encodes a member of the G protein-coupled receptor family. The protein interacts with thromboxane A2 to induce platelet aggregation and regulate hemostasis. A mutation in this gene results in a bleeding disorder. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

TBXA2R Gene-Disease associations (from GenCC):

bleeding diathesis due to thromboxane synthesis deficiency
Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
bleeding disorder, platelet-type, 13, susceptibility to
Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
qualitative platelet defect
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

TBXA2R links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3116118E-5).

BP6

Variant 19-3595925-G-A is Benign according to our data. Variant chr19-3595925-G-A is described in ClinVar as Benign. ClinVar VariationId is 263268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000589966.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	NM_001060.6	MANE Select	c.795C>T	p.Ile265Ile	synonymous	Exon 3 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.795C>T	p.Ile265Ile	synonymous	Exon 3 of 4	NP_963998.2	P21731-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBXA2R	ENST00000589966.1	TSL:1	c.406C>T	p.Arg136Cys	missense	Exon 2 of 2	ENSP00000468145.1	K7ER80
TBXA2R	ENST00000375190.10	TSL:1 MANE Select	c.795C>T	p.Ile265Ile	synonymous	Exon 3 of 3	ENSP00000364336.4	P21731-3
TBXA2R	ENST00000411851.3	TSL:2	c.795C>T	p.Ile265Ile	synonymous	Exon 3 of 4	ENSP00000393333.2	P21731-2

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23706

AN:

152060

Hom.:

2809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0592

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.607

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.148

Gnomad MID

AF:

0.197

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.168

GnomAD2 exomes

AF:

0.223

AC:

45836

AN:

205122

AF XY:

0.216

show subpopulations

Gnomad AFR exome

AF:

0.0512

Gnomad AMR exome

AF:

0.380

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.605

Gnomad FIN exome

AF:

0.145

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.170

AC:

244978

AN:

1438112

Hom.:

26526

Cov.:

AF XY:

0.171

AC XY:

122204

AN XY:

713250

show subpopulations

African (AFR)

AF:

0.0522

AC:

1731

AN:

33170

American (AMR)

AF:

0.359

AC:

14685

AN:

40910

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

6306

AN:

25578

East Asian (EAS)

AF:

0.625

AC:

24046

AN:

38488

South Asian (SAS)

AF:

0.187

AC:

15526

AN:

82970

European-Finnish (FIN)

AF:

0.147

AC:

7409

AN:

50394

Middle Eastern (MID)

AF:

0.207

AC:

1107

AN:

5340

European-Non Finnish (NFE)

AF:

0.148

AC:

163110

AN:

1101858

Other (OTH)

AF:

0.186

AC:

11058

AN:

59404

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

12787

25574

38360

51147

63934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6100

12200

18300

24400

30500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.156

AC:

23712

AN:

152178

Hom.:

2815

Cov.:

AF XY:

0.160

AC XY:

11904

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0590

AC:

2452

AN:

41550

American (AMR)

AF:

0.250

AC:

3831

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

860

AN:

3472

East Asian (EAS)

AF:

0.607

AC:

3128

AN:

5152

South Asian (SAS)

AF:

0.200

AC:

965

AN:

4818

European-Finnish (FIN)

AF:

0.148

AC:

1570

AN:

10610

Middle Eastern (MID)

AF:

0.205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.151

AC:

10238

AN:

67964

Other (OTH)

AF:

0.166

AC:

349

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

922

1843

2765

3686

4608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.161

Hom.:

5329

Bravo

AF:

0.166

TwinsUK

AF:

0.142

AC:

526

ALSPAC

AF:

0.153

AC:

588

ESP6500AA

AF:

0.0552

AC:

226

ESP6500EA

AF:

0.153

AC:

1276

ExAC

AF:

0.192

AC:

22779

Asia WGS

AF:

0.302

AC:

1049

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

6.4

(source)

DANN

Benign

0.87

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.41

MetaRNN

Benign

0.000013

PhyloP100

0.25

Sift4G

Benign

0.087

Vest4

0.20

GERP RS

-0.79

Mutation Taster

=61/39

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over