rs4523

Variant names:

• chr19-3595796-A-G
• rs4523
• ENST00000589966.1:c.535T>C
• TBXA2R p.Tyr179His

Your query was ambiguous. Multiple possible variants found:

• chr19-3595796-A-G
• chr19-3595796-A-C
• chr19-3595796-A-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.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. 9/12 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:5
• Conservation: PhyloP100: 2.82
• Publications: 70 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=1.0298587E-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 VariationId 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.

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.924T>C	p.Tyr308Tyr	synonymous	Exon 3 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.924T>C	p.Tyr308Tyr	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.535T>C	p.Tyr179His	missense	Exon 2 of 2	ENSP00000468145.1	K7ER80
	TBXA2R	ENST00000375190.10	TSL:1 MANE Select	c.924T>C	p.Tyr308Tyr	synonymous	Exon 3 of 3	ENSP00000364336.4	P21731-3
	TBXA2R	ENST00000411851.3	TSL:2	c.924T>C	p.Tyr308Tyr	synonymous	Exon 3 of 4	ENSP00000393333.2	P21731-2

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

GnomAD2 exomes AF: 0.564 AC: 135033 AN: 239524 AF XY: 0.568

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 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

African (AFR) AF: 0.789 AC: 26403 AN: 33444

American (AMR) AF: 0.402 AC: 17783 AN: 44238

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 16070 AN: 26056

East Asian (EAS) AF: 0.174 AC: 6889 AN: 39598

South Asian (SAS) AF: 0.481 AC: 41210 AN: 85718

European-Finnish (FIN) AF: 0.627 AC: 32895 AN: 52440

Middle Eastern (MID) AF: 0.663 AC: 3822 AN: 5766

European-Non Finnish (NFE) AF: 0.655 AC: 726969 AN: 1110634

Other (OTH) AF: 0.606 AC: 36495 AN: 60194

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

African (AFR) AF: 0.778 AC: 32284 AN: 41508

American (AMR) AF: 0.535 AC: 8177 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2168 AN: 3468

East Asian (EAS) AF: 0.180 AC: 929 AN: 5162

South Asian (SAS) AF: 0.462 AC: 2229 AN: 4824

European-Finnish (FIN) AF: 0.627 AC: 6639 AN: 10590

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44302 AN: 67964

Other (OTH) AF: 0.652 AC: 1380 AN: 2116

Alfa AF: 0.651 Hom.: 70273

Bravo AF: 0.646

Asia WGS AF: 0.395 AC: 1377 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	0.15
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
PhyloP100		2.8
Sift4G	Benign	0.20	T
Mutation Taster		=88/12	polymorphism (auto)

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

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

Other links and lift over

dbSNP: rs4523;

hg19: chr19-3595794;

COSMIC: COSV59258345;

COSMIC: COSV59258345;