rs34486470

chr19-3595008-A-G

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.*680T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,420,466 control chromosomes in the GnomAD database, including 7,354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (910 hom., cov: 32)
  • Exomes 𝑓: 0.10 (6444 hom.)
• Consequence: TBXA2R NM_001060.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.320

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=0.0019531548).
• BP6: Variant 19-3595008-A-G is Benign according to our data. Variant chr19-3595008-A-G is described in ClinVar as [Benign]. Clinvar id is 263265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBXA2R	NM_001060.6	c.*680T>C		3_prime_UTR_variant	3/3	ENST00000375190.10
TBXA2R	NM_201636.3	c.1052T>C	p.Leu351Pro	missense_variant	4/4
TBXA2R	XM_011528214.3	c.*680T>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBXA2R	ENST00000375190.10	c.*680T>C		3_prime_UTR_variant	3/3	1	NM_001060.6	P1
TBXA2R	ENST00000589966.1	c.*543T>C		3_prime_UTR_variant	2/2	1
TBXA2R	ENST00000411851.3	c.1052T>C	p.Leu351Pro	missense_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.106 AC: 15830 AN: 149250 Hom.: 908 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0795

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.0667

Gnomad EAS AF: 0.0228

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.108

GnomAD3 exomes AF: 0.0840 AC: 11530 AN: 137202 Hom.: 553 AF XY: 0.0848 AC XY: 6294 AN XY: 74252

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.0552

Gnomad ASJ exome AF: 0.0708

Gnomad EAS exome AF: 0.0253

Gnomad SAS exome AF: 0.0774

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.0999 AC: 127038 AN: 1271112 Hom.: 6444 Cov.: 19 AF XY: 0.0999 AC XY: 62967 AN XY: 630406

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.0627

Gnomad4 ASJ exome AF: 0.0733

Gnomad4 EAS exome AF: 0.0161

Gnomad4 SAS exome AF: 0.0779

Gnomad4 FIN exome AF: 0.128

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.0981

GnomAD4 genome AF: 0.106 AC: 15832 AN: 149354 Hom.: 910 Cov.: 32 AF XY: 0.105 AC XY: 7654 AN XY: 72804

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0873

Gnomad4 ASJ AF: 0.0667

Gnomad4 EAS AF: 0.0227

Gnomad4 SAS AF: 0.0803

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0505 Hom.: 55

Bravo AF: 0.103

TwinsUK AF: 0.103 AC: 383

ALSPAC AF: 0.0999 AC: 385

ESP6500AA AF: 0.106 AC: 187

ESP6500EA AF: 0.0716 AC: 246

ExAC AF: 0.0776 AC: 1664

Asia WGS AF: 0.0520 AC: 180 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

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	5.4
Dann	Benign	0.92
Eigen	Benign	-0.76
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.0050
Sift	Uncertain	0.025	D
Sift4G	Benign	0.29	T
Vest4		0.11
MPC		2.0
ClinPred		0.0048	T
GERP RS		0.23
gMVP		0.29

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: rs34486470; hg19: chr19-3595006;