rs1131882

Variant names:

• chr19-3595925-G-A
• rs1131882
• ENST00000589966.1:c.406C>T
• TBXA2R p.Arg136Cys

Your query was ambiguous. Multiple possible variants found:

• chr19-3595925-G-A
• chr19-3595925-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.249
• Publications: 64 publications found

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 disorder, platelet-type, 13, susceptibility to

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
• qualitative platelet defect

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• bleeding diathesis due to thromboxane synthesis deficiency

  Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

Sel.	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.: 32

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

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.: 41 AF XY: 0.171 AC XY: 122204 AN XY: 713250

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

GnomAD4 genome AF: 0.156 AC: 23712 AN: 152178 Hom.: 2815 Cov.: 32 AF XY: 0.160 AC XY: 11904 AN XY: 74404

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: 60 AN: 292

European-Non Finnish (NFE) AF: 0.151 AC: 10238 AN: 67964

Other (OTH) AF: 0.166 AC: 349 AN: 2108

Alfa AF: 0.161 Hom.: 5329

Bravo AF: 0.166

Asia WGS AF: 0.302 AC: 1049 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	6.4
DANN	Benign	0.87
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.000013	T
PhyloP100		0.25
Sift4G	Benign	0.087	T
Mutation Taster		=61/39	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1131882;

hg19: chr19-3595923;

COSMIC: COSV59260740;

COSMIC: COSV59260740;