19-3595034-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001060.6(TBXA2R):c.*654G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 1,123,478 control chromosomes in the GnomAD database, including 142,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (15501 hom., cov: 25)
  • Exomes 𝑓: 0.50 (126612 hom.)
• Consequence: TBXA2R NM_001060.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.95

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 (BayesDel_noAF=-1.02).
• BP6: Variant 19-3595034-C-T is Benign according to our data. Variant chr19-3595034-C-T is described in ClinVar as [Benign]. Clinvar id is 263264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBXA2R	NM_001060.6	c.*654G>A		3_prime_UTR_variant	3/3	ENST00000375190.10
TBXA2R	NM_201636.3	c.1026G>A	p.Thr342=	synonymous_variant	4/4
TBXA2R	XM_011528214.3	c.*654G>A		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBXA2R	ENST00000375190.10	c.*654G>A		3_prime_UTR_variant	3/3	1	NM_001060.6	P1
TBXA2R	ENST00000589966.1	c.*517G>A		3_prime_UTR_variant	2/2	1
TBXA2R	ENST00000411851.3	c.1026G>A	p.Thr342=	synonymous_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.461 AC: 65582 AN: 142368 Hom.: 15496 Cov.: 25

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.499

GnomAD3 exomes AF: 0.426 AC: 56865 AN: 133342 Hom.: 13295 AF XY: 0.431 AC XY: 31231 AN XY: 72442

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.321

Gnomad ASJ exome AF: 0.539

Gnomad EAS exome AF: 0.145

Gnomad SAS exome AF: 0.373

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.542

Gnomad OTH exome AF: 0.477

GnomAD4 exome AF: 0.501 AC: 491742 AN: 981030 Hom.: 126612 Cov.: 13 AF XY: 0.498 AC XY: 248368 AN XY: 499166

Gnomad4 AFR exome AF: 0.324

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.548

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.512

Gnomad4 NFE exome AF: 0.540

Gnomad4 OTH exome AF: 0.483

GnomAD4 genome AF: 0.461 AC: 65601 AN: 142448 Hom.: 15501 Cov.: 25 AF XY: 0.456 AC XY: 31557 AN XY: 69276

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.498

Alfa AF: 0.495 Hom.: 3419

Bravo AF: 0.427

Asia WGS AF: 0.289 AC: 1008 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

This variant is associated with the following publications: (PMID: 16953279) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.68
Dann	Benign	0.76

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: rs5758; hg19: chr19-3595032; COSMIC: COSV59258203; COSMIC: COSV59258203;