rs1131882

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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. 8/11 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. R136H) 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:4
• Conservation: PhyloP100: 0.249

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBXA2R	NM_001060.6	c.795C>T	p.Ile265=	synonymous_variant	3/3	ENST00000375190.10	NP_001051.1
TBXA2R	NM_201636.3	c.795C>T	p.Ile265=	synonymous_variant	3/4		NP_963998.2
TBXA2R	XM_011528214.3	c.795C>T	p.Ile265=	synonymous_variant	4/4		XP_011526516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBXA2R	ENST00000589966.1	c.406C>T	p.Arg136Cys	missense_variant	2/2	1		ENSP00000468145
TBXA2R	ENST00000375190.10	c.795C>T	p.Ile265=	synonymous_variant	3/3	1	NM_001060.6	ENSP00000364336	P1
TBXA2R	ENST00000411851.3	c.795C>T	p.Ile265=	synonymous_variant	3/4	2		ENSP00000393333

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

GnomAD3 exomes AF: 0.223 AC: 45836 AN: 205122 Hom.: 7117 AF XY: 0.216 AC XY: 24087 AN XY: 111744

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 SAS exome AF: 0.182

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

Gnomad4 AFR exome AF: 0.0522

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.247

Gnomad4 EAS exome AF: 0.625

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.186

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

Gnomad4 AFR AF: 0.0590

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.166

Alfa AF: 0.156 Hom.: 1113

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

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	This variant is associated with the following publications: (PMID: 11922633, 23517037) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
MutationTaster	Benign	0.00077	P;P;P
Sift4G	Benign	0.087	T
Vest4		0.20
GERP RS		-0.79

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

LitVar

Other links and lift over

dbSNP: rs1131882; hg19: chr19-3595923; COSMIC: COSV59260740; COSMIC: COSV59260740;