rs41708

Variant names:

• chr7-139847047-A-C
• rs41708
• NM_001061.7:c.89+17568A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-139847047-A-C
• chr7-139847047-A-T

Variant summary

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

The NM_001061.7(TBXAS1):​c.89+17568A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 152,088 control chromosomes in the GnomAD database, including 57,632 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 0.86 (57632 hom., cov: 30)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546
• Publications: 15 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXAS1	NM_001061.7	c.89+17568A>C		intron_variant	Intron 1 of 12	ENST00000448866.7	NP_001052.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXAS1	ENST00000448866.7	c.89+17568A>C		intron_variant	Intron 1 of 12	1	NM_001061.7	ENSP00000402536.3

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131130 AN: 151970 Hom.: 57621 Cov.: 30

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.956

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.863 AC: 131183 AN: 152088 Hom.: 57632 Cov.: 30 AF XY: 0.861 AC XY: 64013 AN XY: 74354

African (AFR) AF: 0.709 AC: 29360 AN: 41400

American (AMR) AF: 0.779 AC: 11908 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3254 AN: 3472

East Asian (EAS) AF: 0.780 AC: 4031 AN: 5168

South Asian (SAS) AF: 0.919 AC: 4425 AN: 4816

European-Finnish (FIN) AF: 0.956 AC: 10148 AN: 10616

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.956 AC: 65052 AN: 68022

Other (OTH) AF: 0.880 AC: 1856 AN: 2110

Alfa AF: 0.920 Hom.: 135966

Bravo AF: 0.838

Asia WGS AF: 0.833 AC: 2893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.65
PhyloP100		0.55
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: rs41708; hg19: chr7-139546846;