rs6478565

Positions:

• chr9-122386353-A-G
• chr9-122386353-A-T

Variant summary

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

The NM_000962.4(PTGS1):​c.1010-93A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,366,924 control chromosomes in the GnomAD database, including 33,395 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 0.30 (10110 hom., cov: 31)
  • Exomes 𝑓: 0.18 (23285 hom.)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690

Genes affected

PTGS1 (HGNC:9604): (prostaglandin-endoperoxide synthase 1) This is one of two genes encoding similar enzymes that catalyze the conversion of arachidonate to prostaglandin. The encoded protein regulates angiogenesis in endothelial cells, and is inhibited by nonsteroidal anti-inflammatory drugs such as aspirin. Based on its ability to function as both a cyclooxygenase and as a peroxidase, the encoded protein has been identified as a moonlighting protein. The protein may promote cell proliferation during tumor progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2021]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGS1	NM_000962.4	c.1010-93A>G		intron_variant		ENST00000362012.7	NP_000953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGS1	ENST00000362012.7	c.1010-93A>G		intron_variant		1	NM_000962.4	ENSP00000354612	P1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45974 AN: 151932 Hom.: 10068 Cov.: 31

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0675

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.178 AC: 216490 AN: 1214874 Hom.: 23285 AF XY: 0.178 AC XY: 107805 AN XY: 606108

Gnomad4 AFR exome AF: 0.634

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.0539

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.303 AC: 46079 AN: 152050 Hom.: 10110 Cov.: 31 AF XY: 0.298 AC XY: 22186 AN XY: 74334

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0675

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.285

Alfa AF: 0.188 Hom.: 6271

Bravo AF: 0.322

Asia WGS AF: 0.196 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6478565; hg19: chr9-125148632;