rs6464435

Variant names:

• chr7-139891932-C-A
• rs6464435
• NM_001061.7:c.236+16295C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-139891932-C-A
• chr7-139891932-C-G

Variant summary

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

The NM_001061.7(TBXAS1):​c.236+16295C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,008 control chromosomes in the GnomAD database, including 11,466 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 0.38 (11466 hom., cov: 31)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXAS1	NM_001061.7	c.236+16295C>A		intron_variant	Intron 3 of 12	ENST00000448866.7	NP_001052.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXAS1	ENST00000448866.7	c.236+16295C>A		intron_variant	Intron 3 of 12	1	NM_001061.7	ENSP00000402536.3

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57731 AN: 151890 Hom.: 11456 Cov.: 31

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.380 AC: 57770 AN: 152008 Hom.: 11466 Cov.: 31 AF XY: 0.383 AC XY: 28485 AN XY: 74304

African (AFR) AF: 0.473 AC: 19609 AN: 41444

American (AMR) AF: 0.451 AC: 6899 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1438 AN: 3470

East Asian (EAS) AF: 0.410 AC: 2119 AN: 5166

South Asian (SAS) AF: 0.492 AC: 2367 AN: 4808

European-Finnish (FIN) AF: 0.322 AC: 3406 AN: 10566

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20597 AN: 67952

Other (OTH) AF: 0.385 AC: 814 AN: 2114

Alfa AF: 0.328 Hom.: 14267

Bravo AF: 0.392

Asia WGS AF: 0.436 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.033
DANN	Benign	0.41
PhyloP100		-1.4
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: rs6464435; hg19: chr7-139591731;