19-3604301-T-C

Variant names:

• chr19-3604301-T-C
• rs2238631
• NM_001060.6:c.-84+2229A>G

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+2229A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,030 control chromosomes in the GnomAD database, including 53,493 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 0.83 (53493 hom., cov: 32)
• Consequence: TBXA2R NM_001060.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579
• Publications: 10 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):

• bleeding diathesis due to thromboxane synthesis deficiency

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• bleeding disorder, platelet-type, 13, susceptibility to

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
• qualitative platelet defect

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.954 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	NM_001060.6	MANE Select	c.-84+2229A>G		intron	N/A	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.-84+2229A>G		intron	N/A	NP_963998.2	P21731-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	ENST00000375190.10	TSL:1 MANE Select	c.-84+2229A>G		intron	N/A	ENSP00000364336.4	P21731-3
	TBXA2R	ENST00000882308.1		c.-734A>G		5_prime_UTR	Exon 1 of 3	ENSP00000552367.1
	TBXA2R	ENST00000411851.3	TSL:2	c.-84+2229A>G		intron	N/A	ENSP00000393333.2	P21731-2

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126713 AN: 151912 Hom.: 53447 Cov.: 32

Gnomad AFR AF: 0.962

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.841

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

GnomAD4 genome AF: 0.834 AC: 126809 AN: 152030 Hom.: 53493 Cov.: 32 AF XY: 0.829 AC XY: 61603 AN XY: 74290

African (AFR) AF: 0.962 AC: 39952 AN: 41524

American (AMR) AF: 0.767 AC: 11732 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3034 AN: 3468

East Asian (EAS) AF: 0.772 AC: 3972 AN: 5148

South Asian (SAS) AF: 0.663 AC: 3198 AN: 4824

European-Finnish (FIN) AF: 0.774 AC: 8179 AN: 10566

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54040 AN: 67894

Other (OTH) AF: 0.833 AC: 1755 AN: 2108

Alfa AF: 0.818 Hom.: 114234

Bravo AF: 0.843

Asia WGS AF: 0.674 AC: 2343 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.9
DANN	Benign	0.24
PhyloP100		0.58
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: rs2238631; hg19: chr19-3604299;