19-3595374-G-A

Position:

• chr19-3595374-G-A

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.*314C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,372,488 control chromosomes in the GnomAD database, including 939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (535 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (404 hom.)
• Consequence: TBXA2R NM_001060.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.321

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=-1.03).
• BP6: Variant 19-3595374-G-A is Benign according to our data. Variant chr19-3595374-G-A is described in ClinVar as [Benign]. Clinvar id is 1293885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBXA2R	NM_001060.6	c.*314C>T		3_prime_UTR_variant	3/3	ENST00000375190.10	NP_001051.1
TBXA2R	XM_011528214.3	c.*314C>T		3_prime_UTR_variant	4/4		XP_011526516.1
TBXA2R	NM_201636.3	c.984-298C>T		intron_variant			NP_963998.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBXA2R	ENST00000375190.10	c.*314C>T		3_prime_UTR_variant	3/3	1	NM_001060.6	ENSP00000364336	P1
TBXA2R	ENST00000589966.1	c.*177C>T		3_prime_UTR_variant	2/2	1		ENSP00000468145
TBXA2R	ENST00000411851.3	c.984-298C>T		intron_variant		2		ENSP00000393333

Frequencies

GnomAD3 genomes AF: 0.0466 AC: 7069 AN: 151796 Hom.: 519 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00239

Gnomad OTH AF: 0.0293

GnomAD4 exome AF: 0.00627 AC: 7658 AN: 1220576 Hom.: 404 Cov.: 28 AF XY: 0.00585 AC XY: 3423 AN XY: 585320

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.00923

Gnomad4 ASJ exome AF: 0.00198

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000376

Gnomad4 FIN exome AF: 0.000219

Gnomad4 NFE exome AF: 0.00234

Gnomad4 OTH exome AF: 0.0125

GnomAD4 genome AF: 0.0469 AC: 7131 AN: 151912 Hom.: 535 Cov.: 32 AF XY: 0.0463 AC XY: 3439 AN XY: 74282

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0132

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00239

Gnomad4 OTH AF: 0.0290

Alfa AF: 0.0258 Hom.: 48

Bravo AF: 0.0530

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 07, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.3
DANN	Benign	0.45

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: rs8113664; hg19: chr19-3595372;