NM_001061.7:c.689-105C>A

Variant names:

• chr7-139957529-C-A
• rs3735355
• NM_001061.7:c.689-105C>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.689-105C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0933 in 1,516,642 control chromosomes in the GnomAD database, including 7,759 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 0.079 (712 hom., cov: 31)
  • Exomes 𝑓: 0.095 (7047 hom.)
• Consequence: TBXAS1 NM_001061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42
• Publications: 1 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: G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000305529 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 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.689-105C>A		intron	N/A	NP_001052.3	P24557-1
	TBXAS1	NM_001166253.4		c.827-105C>A		intron	N/A	NP_001159725.2	P24557-3
	TBXAS1	NM_001130966.5		c.689-105C>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.689-105C>A		intron	N/A	ENSP00000402536.3	P24557-1
	TBXAS1	ENST00000336425.10	TSL:1	c.689-105C>A		intron	N/A	ENSP00000338087.7	P24557-1
	TBXAS1	ENST00000425687.5	TSL:1	c.488-105C>A		intron	N/A	ENSP00000388736.1	P24557-2

Frequencies

GnomAD3 genomes AF: 0.0792 AC: 12044 AN: 152030 Hom.: 712 Cov.: 31

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0556

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.0988

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0928

Gnomad OTH AF: 0.0788

GnomAD4 exome AF: 0.0949 AC: 129456 AN: 1364494 Hom.: 7047 AF XY: 0.0951 AC XY: 65017 AN XY: 683416

African (AFR) AF: 0.0159 AC: 503 AN: 31600

American (AMR) AF: 0.0351 AC: 1511 AN: 43104

Ashkenazi Jewish (ASJ) AF: 0.0694 AC: 1753 AN: 25256

East Asian (EAS) AF: 0.229 AC: 8883 AN: 38760

South Asian (SAS) AF: 0.0957 AC: 7981 AN: 83430

European-Finnish (FIN) AF: 0.182 AC: 8269 AN: 45548

Middle Eastern (MID) AF: 0.0745 AC: 414 AN: 5558

European-Non Finnish (NFE) AF: 0.0918 AC: 94901 AN: 1034034

Other (OTH) AF: 0.0916 AC: 5241 AN: 57204

GnomAD4 genome AF: 0.0791 AC: 12039 AN: 152148 Hom.: 712 Cov.: 31 AF XY: 0.0844 AC XY: 6274 AN XY: 74360

African (AFR) AF: 0.0184 AC: 763 AN: 41552

American (AMR) AF: 0.0555 AC: 848 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0749 AC: 260 AN: 3470

East Asian (EAS) AF: 0.218 AC: 1123 AN: 5162

South Asian (SAS) AF: 0.0985 AC: 474 AN: 4814

European-Finnish (FIN) AF: 0.194 AC: 2048 AN: 10560

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0928 AC: 6306 AN: 67980

Other (OTH) AF: 0.0794 AC: 168 AN: 2116

Alfa AF: 0.0833 Hom.: 86

Bravo AF: 0.0654

Asia WGS AF: 0.138 AC: 480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.016
DANN	Benign	0.57
PhyloP100		-2.4
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: rs3735355; hg19: chr7-139657328; COSMIC: COSV54956691; COSMIC: COSV54956691;