rs5745

chr19-3600392-G-Achr19-3600392-G-Cchr19-3600392-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001060.6(TBXA2R):c.243C>T(p.Thr81=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 1,613,254 control chromosomes in the GnomAD database, including 7,579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (892 hom., cov: 32)
  • Exomes 𝑓: 0.094 (6687 hom.)
• Consequence: TBXA2R NM_001060.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.73

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 19-3600392-G-A is Benign according to our data. Variant chr19-3600392-G-A is described in ClinVar as [Benign]. Clinvar id is 263266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.73 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBXA2R	NM_001060.6	c.243C>T	p.Thr81=	synonymous_variant	2/3	ENST00000375190.10
TBXA2R	NM_201636.3	c.243C>T	p.Thr81=	synonymous_variant	2/4
TBXA2R	XM_011528214.3	c.243C>T	p.Thr81=	synonymous_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBXA2R	ENST00000375190.10	c.243C>T	p.Thr81=	synonymous_variant	2/3	1	NM_001060.6	P1
TBXA2R	ENST00000589966.1	c.243C>T	p.Thr81=	synonymous_variant	1/2	1
TBXA2R	ENST00000411851.3	c.243C>T	p.Thr81=	synonymous_variant	2/4	2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15313 AN: 152070 Hom.: 891 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.0829

Gnomad ASJ AF: 0.0649

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.0684

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0976

Gnomad OTH AF: 0.0975

GnomAD3 exomes AF: 0.0814 AC: 20014 AN: 245816 Hom.: 929 AF XY: 0.0822 AC XY: 11017 AN XY: 134074

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.0505

Gnomad ASJ exome AF: 0.0658

Gnomad EAS exome AF: 0.0264

Gnomad SAS exome AF: 0.0637

Gnomad FIN exome AF: 0.0829

Gnomad NFE exome AF: 0.0976

Gnomad OTH exome AF: 0.0907

GnomAD4 exome AF: 0.0936 AC: 136795 AN: 1461066 Hom.: 6687 Cov.: 33 AF XY: 0.0933 AC XY: 67785 AN XY: 726864

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.0550

Gnomad4 ASJ exome AF: 0.0635

Gnomad4 EAS exome AF: 0.0166

Gnomad4 SAS exome AF: 0.0640

Gnomad4 FIN exome AF: 0.0806

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.0883

GnomAD4 genome AF: 0.101 AC: 15317 AN: 152188 Hom.: 892 Cov.: 32 AF XY: 0.0981 AC XY: 7303 AN XY: 74410

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0828

Gnomad4 ASJ AF: 0.0649

Gnomad4 EAS AF: 0.0241

Gnomad4 SAS AF: 0.0682

Gnomad4 FIN AF: 0.0778

Gnomad4 NFE AF: 0.0975

Gnomad4 OTH AF: 0.0965

Alfa AF: 0.0959 Hom.: 280

Bravo AF: 0.102

Asia WGS AF: 0.0450 AC: 157 AN: 3478

EpiCase AF: 0.102

EpiControl AF: 0.106

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	1.3
Dann	Benign	0.92

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: rs5745; hg19: chr19-3600390; COSMIC: COSV64343573; COSMIC: COSV64343573;