19-3595413-T-C

Position:

• chr19-3595413-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000375190.10(TBXA2R):​c.*275A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,392,400 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0084 (18 hom., cov: 33)
  • Exomes 𝑓: 0.00077 (9 hom.)
• Consequence: TBXA2R ENST00000375190.10 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.726

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=-0.99).
• BP6: Variant 19-3595413-T-C is Benign according to our data. Variant chr19-3595413-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1218080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00836 (1266/151366) while in subpopulation AFR AF= 0.0284 (1175/41352). AF 95% confidence interval is 0.0271. There are 18 homozygotes in gnomad4. There are 617 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1266 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBXA2R	NM_001060.6	c.*275A>G		3_prime_UTR_variant	3/3	ENST00000375190.10	NP_001051.1
TBXA2R	XM_011528214.3	c.*275A>G		3_prime_UTR_variant	4/4		XP_011526516.1
TBXA2R	NM_201636.3	c.983+324A>G		intron_variant			NP_963998.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBXA2R	ENST00000375190.10	c.*275A>G		3_prime_UTR_variant	3/3	1	NM_001060.6	ENSP00000364336	P1
TBXA2R	ENST00000589966.1	c.*138A>G		3_prime_UTR_variant	2/2	1		ENSP00000468145
TBXA2R	ENST00000411851.3	c.983+324A>G		intron_variant		2		ENSP00000393333

Frequencies

GnomAD3 genomes AF: 0.00817 AC: 1236 AN: 151276 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00316

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00771

GnomAD4 exome AF: 0.000765 AC: 950 AN: 1241034 Hom.: 9 Cov.: 40 AF XY: 0.000711 AC XY: 424 AN XY: 596412

Gnomad4 AFR exome AF: 0.0247

Gnomad4 AMR exome AF: 0.00260

Gnomad4 ASJ exome AF: 0.00194

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000142

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000594

Gnomad4 OTH exome AF: 0.00221

GnomAD4 genome AF: 0.00836 AC: 1266 AN: 151366 Hom.: 18 Cov.: 33 AF XY: 0.00835 AC XY: 617 AN XY: 73920

Gnomad4 AFR AF: 0.0284

Gnomad4 AMR AF: 0.00315

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00763

Alfa AF: 0.00548 Hom.: 2

Bravo AF: 0.00878

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.44

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: rs5754; hg19: chr19-3595411;