chr9-122378047-G-A

Variant names:

• chr9-122378047-G-A
• rs876567
• NM_000962.4:c.211+32G>A

Variant summary

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

The NM_000962.4(PTGS1):​c.211+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 1,581,350 control chromosomes in the GnomAD database, including 290 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 0.025 (141 hom., cov: 33)
  • Exomes 𝑓: 0.0056 (149 hom.)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.94
• Publications: 3 publications found

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]

PTGS1 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 12

  Inheritance: SD Classification: LIMITED Submitted by: ClinGen

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 (AFR) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000962.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS1	NM_000962.4	MANE Select	c.211+32G>A		intron	N/A	NP_000953.2
	PTGS1	NM_080591.3		c.211+32G>A		intron	N/A	NP_542158.1
	PTGS1	NM_001271164.2		c.211+32G>A		intron	N/A	NP_001258093.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS1	ENST00000362012.7	TSL:1 MANE Select	c.211+32G>A		intron	N/A	ENSP00000354612.2
	PTGS1	ENST00000223423.8	TSL:1	c.211+32G>A		intron	N/A	ENSP00000223423.4
	PTGS1	ENST00000619306.5	TSL:5	c.211+32G>A		intron	N/A	ENSP00000483540.2

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3799 AN: 152182 Hom.: 141 Cov.: 33

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00344

Gnomad OTH AF: 0.0225

GnomAD2 exomes AF: 0.00811 AC: 1993 AN: 245886 AF XY: 0.00646

Gnomad AFR exome AF: 0.0804

Gnomad AMR exome AF: 0.00574

Gnomad ASJ exome AF: 0.00120

Gnomad EAS exome AF: 0.00152

Gnomad FIN exome AF: 0.000633

Gnomad NFE exome AF: 0.00299

Gnomad OTH exome AF: 0.00560

GnomAD4 exome AF: 0.00556 AC: 7947 AN: 1429050 Hom.: 149 Cov.: 28 AF XY: 0.00511 AC XY: 3643 AN XY: 712902

African (AFR) AF: 0.0858 AC: 2809 AN: 32752

American (AMR) AF: 0.00574 AC: 256 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00139 AC: 36 AN: 25928

East Asian (EAS) AF: 0.00142 AC: 56 AN: 39576

South Asian (SAS) AF: 0.00204 AC: 175 AN: 85674

European-Finnish (FIN) AF: 0.000792 AC: 38 AN: 47968

Middle Eastern (MID) AF: 0.0110 AC: 63 AN: 5702

European-Non Finnish (NFE) AF: 0.00371 AC: 4031 AN: 1087334

Other (OTH) AF: 0.00812 AC: 483 AN: 59496

GnomAD4 genome AF: 0.0250 AC: 3811 AN: 152300 Hom.: 141 Cov.: 33 AF XY: 0.0241 AC XY: 1798 AN XY: 74472

African (AFR) AF: 0.0805 AC: 3343 AN: 41552

American (AMR) AF: 0.0101 AC: 155 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5176

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4824

European-Finnish (FIN) AF: 0.000376 AC: 4 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00345 AC: 235 AN: 68028

Other (OTH) AF: 0.0222 AC: 47 AN: 2114

Alfa AF: 0.0164 Hom.: 31

Bravo AF: 0.0280

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.58
DANN	Benign	0.55
PhyloP100		-2.9
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: rs876567; hg19: chr9-125140326;