19-3595406-C-G

Position:

• chr19-3595406-C-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.*282G>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 0.00479 in 1,393,842 control chromosomes in the GnomAD database, including 254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (147 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (107 hom.)
• Consequence: TBXA2R NM_001060.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.50

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=-0.87).
• BP6: Variant 19-3595406-C-G is Benign according to our data. Variant chr19-3595406-C-G is described in ClinVar as [Benign]. Clinvar id is 1252629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.083 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBXA2R	NM_001060.6	c.*282G>C		3_prime_UTR_variant	3/3	ENST00000375190.10	NP_001051.1
TBXA2R	XM_011528214.3	c.*282G>C		3_prime_UTR_variant	4/4		XP_011526516.1
TBXA2R	NM_201636.3	c.984-330G>C		intron_variant			NP_963998.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBXA2R	ENST00000375190.10	c.*282G>C		3_prime_UTR_variant	3/3	1	NM_001060.6	ENSP00000364336	P1
TBXA2R	ENST00000589966.1	c.*145G>C		3_prime_UTR_variant	2/2	1		ENSP00000468145
TBXA2R	ENST00000411851.3	c.984-330G>C		intron_variant		2		ENSP00000393333

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3664 AN: 152088 Hom.: 142 Cov.: 32

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0149

GnomAD4 exome AF: 0.00240 AC: 2978 AN: 1241638 Hom.: 107 Cov.: 40 AF XY: 0.00222 AC XY: 1327 AN XY: 596644

Gnomad4 AFR exome AF: 0.0872

Gnomad4 AMR exome AF: 0.00520

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000304

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000128

Gnomad4 OTH exome AF: 0.00586

GnomAD4 genome AF: 0.0243 AC: 3693 AN: 152204 Hom.: 147 Cov.: 32 AF XY: 0.0241 AC XY: 1790 AN XY: 74424

Gnomad4 AFR AF: 0.0854

Gnomad4 AMR AF: 0.00621

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0182 Hom.: 9

Bravo AF: 0.0275

Asia WGS AF: 0.00751 AC: 26 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	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.67

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: rs8100569; hg19: chr19-3595404;