chr7-140018102-T-A

Variant names:

• chr7-140018102-T-A
• rs10242928
• NM_001061.7:c.1527+269T>A

Variant summary

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

The NM_001061.7(TBXAS1):​c.1527+269T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 152,284 control chromosomes in the GnomAD database, including 672 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 0.090 (672 hom., cov: 33)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.36
• 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: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXAS1	NM_001061.7	c.1527+269T>A		intron_variant	Intron 12 of 12	ENST00000448866.7	NP_001052.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXAS1	ENST00000448866.7	c.1527+269T>A		intron_variant	Intron 12 of 12	1	NM_001061.7	ENSP00000402536.3

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13694 AN: 152166 Hom.: 672 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0821

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0354

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0921

Gnomad OTH AF: 0.0956

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

GnomAD4 genome AF: 0.0900 AC: 13704 AN: 152284 Hom.: 672 Cov.: 33 AF XY: 0.0887 AC XY: 6604 AN XY: 74460

African (AFR) AF: 0.108 AC: 4489 AN: 41554

American (AMR) AF: 0.0820 AC: 1255 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0651 AC: 226 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5196

South Asian (SAS) AF: 0.0352 AC: 170 AN: 4824

European-Finnish (FIN) AF: 0.0916 AC: 972 AN: 10612

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0921 AC: 6266 AN: 68004

Other (OTH) AF: 0.0946 AC: 200 AN: 2114

Alfa AF: 0.0835 Hom.: 66

Bravo AF: 0.0900

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.43
DANN	Benign	0.46
PhyloP100		-5.4
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: rs10242928; hg19: chr7-139717902;