rs2267703

Variant names:

• chr7-139987984-G-A
• rs2267703
• NM_001061.7:c.1135-19107G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-139987984-G-A
• chr7-139987984-G-C

Variant summary

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

The NM_001061.7(TBXAS1):​c.1135-19107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,926 control chromosomes in the GnomAD database, including 10,982 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 0.36 (10982 hom., cov: 31)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• Publications: 3 publications found

Genes affected

TBXAS1 (HGNC:11609): (thromboxane A synthase 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostglandin H2 to thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation. The enzyme plays a role in several pathophysiological processes including hemostasis, cardiovascular disease, and stroke. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

TBXAS1 Gene-Disease associations (from GenCC):

• ghosal hematodiaphyseal dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001061.7. 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
	TBXAS1	NM_001061.7	MANE Select	c.1135-19107G>A		intron	N/A	NP_001052.3	P24557-1
	TBXAS1	NM_001166253.4		c.1273-19107G>A		intron	N/A	NP_001159725.2	P24557-3
	TBXAS1	NM_001130966.5		c.1135-19107G>A		intron	N/A	NP_001124438.2	P24557-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXAS1	ENST00000448866.7	TSL:1 MANE Select	c.1135-19107G>A		intron	N/A	ENSP00000402536.3	P24557-1
	TBXAS1	ENST00000336425.10	TSL:1	c.1135-19107G>A		intron	N/A	ENSP00000338087.7	P24557-1
	TBXAS1	ENST00000425687.5	TSL:1	c.934-19107G>A		intron	N/A	ENSP00000388736.1	P24557-2

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55260 AN: 151808 Hom.: 10955 Cov.: 31

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.364 AC: 55313 AN: 151926 Hom.: 10982 Cov.: 31 AF XY: 0.370 AC XY: 27478 AN XY: 74250

African (AFR) AF: 0.344 AC: 14239 AN: 41414

American (AMR) AF: 0.536 AC: 8188 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 897 AN: 3466

East Asian (EAS) AF: 0.782 AC: 4013 AN: 5134

South Asian (SAS) AF: 0.235 AC: 1132 AN: 4812

European-Finnish (FIN) AF: 0.353 AC: 3721 AN: 10544

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21822 AN: 67956

Other (OTH) AF: 0.404 AC: 854 AN: 2116

Alfa AF: 0.337 Hom.: 28858

Bravo AF: 0.387

Asia WGS AF: 0.530 AC: 1839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.63
PhyloP100		-0.090
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2267703;

hg19: chr7-139687783;