rs41721

Variant names:

• chr7-139966397-T-C
• rs41721
• NM_001061.7:c.1134+4164T>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.1134+4164T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,018 control chromosomes in the GnomAD database, including 47,269 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 0.79 (47269 hom., cov: 32)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 4 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: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia

ENSG00000305529 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 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.1134+4164T>C		intron	N/A	NP_001052.3	P24557-1
	TBXAS1	NM_001166253.4		c.1272+4164T>C		intron	N/A	NP_001159725.2	P24557-3
	TBXAS1	NM_001130966.5		c.1134+4164T>C		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.1134+4164T>C		intron	N/A	ENSP00000402536.3	P24557-1
	TBXAS1	ENST00000336425.10	TSL:1	c.1134+4164T>C		intron	N/A	ENSP00000338087.7	P24557-1
	TBXAS1	ENST00000425687.5	TSL:1	c.933+4164T>C		intron	N/A	ENSP00000388736.1	P24557-2

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119323 AN: 151900 Hom.: 47249 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.789

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

GnomAD4 genome AF: 0.785 AC: 119372 AN: 152018 Hom.: 47269 Cov.: 32 AF XY: 0.782 AC XY: 58107 AN XY: 74320

African (AFR) AF: 0.678 AC: 28026 AN: 41360

American (AMR) AF: 0.830 AC: 12696 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2990 AN: 3470

East Asian (EAS) AF: 0.878 AC: 4547 AN: 5178

South Asian (SAS) AF: 0.779 AC: 3759 AN: 4824

European-Finnish (FIN) AF: 0.762 AC: 8055 AN: 10570

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56559 AN: 67992

Other (OTH) AF: 0.786 AC: 1664 AN: 2116

Alfa AF: 0.818 Hom.: 32222

Bravo AF: 0.784

Asia WGS AF: 0.789 AC: 2740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.14
DANN	Benign	0.66
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs41721;

hg19: chr7-139666196;