rs4523

Positions:

• chr19-3595796-A-G

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.535T>C​(p.Tyr179His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,610,200 control chromosomes in the GnomAD database, including 324,213 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (33368 hom., cov: 33)
  • Exomes 𝑓: 0.62 (290845 hom.)
• Consequence: TBXA2R ENST00000589966.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.82

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=1.0298587E-6).
• BP6: Variant 19-3595796-A-G is Benign according to our data. Variant chr19-3595796-A-G is described in ClinVar as [Benign]. Clinvar id is 263269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBXA2R	NM_001060.6	c.924T>C	p.Tyr308Tyr	synonymous_variant	3/3	ENST00000375190.10	NP_001051.1
TBXA2R	NM_201636.3	c.924T>C	p.Tyr308Tyr	synonymous_variant	3/4		NP_963998.2
TBXA2R	XM_011528214.3	c.924T>C	p.Tyr308Tyr	synonymous_variant	4/4		XP_011526516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBXA2R	ENST00000589966.1	c.535T>C	p.Tyr179His	missense_variant	2/2	1		ENSP00000468145.1
TBXA2R	ENST00000375190.10	c.924T>C	p.Tyr308Tyr	synonymous_variant	3/3	1	NM_001060.6	ENSP00000364336.4
TBXA2R	ENST00000411851.3	c.924T>C	p.Tyr308Tyr	synonymous_variant	3/4	2		ENSP00000393333.2

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98634 AN: 151994 Hom.: 33324 Cov.: 33

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.655

GnomAD3 exomes AF: 0.564 AC: 135033 AN: 239524 Hom.: 41042 AF XY: 0.568 AC XY: 74212 AN XY: 130666

Gnomad AFR exome AF: 0.787

Gnomad AMR exome AF: 0.381

Gnomad ASJ exome AF: 0.621

Gnomad EAS exome AF: 0.188

Gnomad SAS exome AF: 0.484

Gnomad FIN exome AF: 0.629

Gnomad NFE exome AF: 0.654

Gnomad OTH exome AF: 0.605

GnomAD4 exome AF: 0.623 AC: 908536 AN: 1458088 Hom.: 290845 Cov.: 103 AF XY: 0.620 AC XY: 449455 AN XY: 725094

Gnomad4 AFR exome AF: 0.789

Gnomad4 AMR exome AF: 0.402

Gnomad4 ASJ exome AF: 0.617

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.481

Gnomad4 FIN exome AF: 0.627

Gnomad4 NFE exome AF: 0.655

Gnomad4 OTH exome AF: 0.606

GnomAD4 genome AF: 0.649 AC: 98729 AN: 152112 Hom.: 33368 Cov.: 33 AF XY: 0.642 AC XY: 47749 AN XY: 74356

Gnomad4 AFR AF: 0.778

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.652

Alfa AF: 0.661 Hom.: 17771

Bravo AF: 0.646

TwinsUK AF: 0.653 AC: 2423

ALSPAC AF: 0.653 AC: 2515

ESP6500AA AF: 0.798 AC: 3482

ESP6500EA AF: 0.655 AC: 5600

ExAC AF: 0.569 AC: 68510

Asia WGS AF: 0.395 AC: 1377 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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	This variant is associated with the following publications: (PMID: 28709878, 10830912) -

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	-0.48	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	9.4
DANN	Benign	0.80
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0000010	T
Sift4G	Benign	0.20	T
Vest4		0.22
GERP RS		3.1

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

LitVar

Other links and lift over

dbSNP: rs4523; hg19: chr19-3595794; COSMIC: COSV59258345; COSMIC: COSV59258345;