19-3604500-A-G

Variant names:

• chr19-3604500-A-G
• rs2238632
• NM_001060.6:c.-84+2030T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001060.6(TBXA2R):​c.-84+2030T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,354 control chromosomes in the GnomAD database, including 14,579 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (14579 hom., cov: 30)
• Consequence: TBXA2R NM_001060.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.80
• Publications: 4 publications found

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]

TBXA2R Gene-Disease associations (from GenCC):

• qualitative platelet defect

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• bleeding diathesis due to thromboxane synthesis deficiency

  Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001060.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	NM_001060.6	MANE Select	c.-84+2030T>C		intron	N/A	NP_001051.1
	TBXA2R	NM_201636.3		c.-84+2030T>C		intron	N/A	NP_963998.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	ENST00000375190.10	TSL:1 MANE Select	c.-84+2030T>C		intron	N/A	ENSP00000364336.4
	TBXA2R	ENST00000411851.3	TSL:2	c.-84+2030T>C		intron	N/A	ENSP00000393333.2

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64280 AN: 151236 Hom.: 14560 Cov.: 30

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.414

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.425 AC: 64344 AN: 151354 Hom.: 14579 Cov.: 30 AF XY: 0.422 AC XY: 31165 AN XY: 73902

African (AFR) AF: 0.550 AC: 22646 AN: 41186

American (AMR) AF: 0.429 AC: 6534 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1420 AN: 3462

East Asian (EAS) AF: 0.680 AC: 3488 AN: 5132

South Asian (SAS) AF: 0.428 AC: 2054 AN: 4802

European-Finnish (FIN) AF: 0.287 AC: 2998 AN: 10462

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.351 AC: 23817 AN: 67768

Other (OTH) AF: 0.410 AC: 863 AN: 2106

Alfa AF: 0.390 Hom.: 1453

Bravo AF: 0.446

Asia WGS AF: 0.465 AC: 1614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.076
DANN	Benign	0.39
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2238632; hg19: chr19-3604498;