rs6971207

Positions:

• chr7-139820264-C-A
• chr7-139820264-C-G
• chr7-139820264-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000336425.10(TBXAS1):​c.-79-9048C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 151,920 control chromosomes in the GnomAD database, including 2,233 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 0.11 (2233 hom., cov: 31)
• Consequence: TBXAS1 ENST00000336425.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBXAS1	NM_001130966.5	c.-79-9048C>A		intron_variant			NP_001124438.2
TBXAS1	NM_001166254.4	c.-113+32838C>A		intron_variant			NP_001159726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBXAS1	ENST00000336425.10	c.-79-9048C>A		intron_variant		1		ENSP00000338087	P1
TBXAS1	ENST00000425687.5	c.-113+32838C>A		intron_variant		1		ENSP00000388736
TBXAS1	ENST00000438104.6	c.-79-9048C>A		intron_variant		5		ENSP00000388612

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17269 AN: 151802 Hom.: 2220 Cov.: 31

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.0268

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.0932

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

GnomAD4 genome AF: 0.114 AC: 17324 AN: 151920 Hom.: 2233 Cov.: 31 AF XY: 0.115 AC XY: 8536 AN XY: 74282

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.0262

Gnomad4 FIN AF: 0.0123

Gnomad4 NFE AF: 0.0125

Gnomad4 OTH AF: 0.0960

Alfa AF: 0.0284 Hom.: 757

Bravo AF: 0.141

Asia WGS AF: 0.175 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.9
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs6971207; hg19: chr7-139520063;