chr19-3604731-A-C

Variant names:

• chr19-3604731-A-C
• rs2238634
• NM_001060.6:c.-84+1799T>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+1799T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,138 control chromosomes in the GnomAD database, including 50,434 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 0.81 (50434 hom., cov: 32)
• Consequence: TBXA2R NM_001060.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXA2R	NM_001060.6	c.-84+1799T>G		intron_variant	Intron 1 of 2	ENST00000375190.10	NP_001051.1
TBXA2R	NM_201636.3	c.-84+1799T>G		intron_variant	Intron 1 of 3		NP_963998.2
TBXA2R	XM_011528214.3	c.-202+1799T>G		intron_variant	Intron 1 of 3		XP_011526516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXA2R	ENST00000375190.10	c.-84+1799T>G		intron_variant	Intron 1 of 2	1	NM_001060.6	ENSP00000364336.4
TBXA2R	ENST00000411851.3	c.-84+1799T>G		intron_variant	Intron 1 of 3	2		ENSP00000393333.2

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123423 AN: 152020 Hom.: 50390 Cov.: 32

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.828

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

GnomAD4 genome AF: 0.812 AC: 123519 AN: 152138 Hom.: 50434 Cov.: 32 AF XY: 0.807 AC XY: 60049 AN XY: 74366

African (AFR) AF: 0.882 AC: 36614 AN: 41512

American (AMR) AF: 0.752 AC: 11504 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3038 AN: 3468

East Asian (EAS) AF: 0.774 AC: 3985 AN: 5150

South Asian (SAS) AF: 0.664 AC: 3205 AN: 4824

European-Finnish (FIN) AF: 0.777 AC: 8234 AN: 10596

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

European-Non Finnish (NFE) AF: 0.798 AC: 54257 AN: 67972

Other (OTH) AF: 0.820 AC: 1735 AN: 2116

Alfa AF: 0.801 Hom.: 13784

Bravo AF: 0.818

Asia WGS AF: 0.669 AC: 2328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.75
PhyloP100		-0.49
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: rs2238634; hg19: chr19-3604729;