NM_000962.4:c.1445-29T>C

Variant names:

• chr9-122392160-T-C
• rs3842801
• NM_000962.4:c.1445-29T>C

Variant summary

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

The NM_000962.4(PTGS1):​c.1445-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 1,545,860 control chromosomes in the GnomAD database, including 2,690 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 0.077 (1394 hom., cov: 31)
  • Exomes 𝑓: 0.011 (1296 hom.)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 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.1445-29T>C		intron	N/A	NP_000953.2
	PTGS1	NM_080591.3		c.1334-29T>C		intron	N/A	NP_542158.1
	PTGS1	NM_001271164.2		c.1301-29T>C		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.1445-29T>C		intron	N/A	ENSP00000354612.2
	PTGS1	ENST00000223423.8	TSL:1	c.1334-29T>C		intron	N/A	ENSP00000223423.4
	PTGS1	ENST00000619306.5	TSL:5	c.1301-29T>C		intron	N/A	ENSP00000483540.2

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11688 AN: 152096 Hom.: 1387 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0319

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00381

Gnomad OTH AF: 0.0704

GnomAD2 exomes AF: 0.0249 AC: 5070 AN: 203752 AF XY: 0.0200

Gnomad AFR exome AF: 0.266

Gnomad AMR exome AF: 0.0190

Gnomad ASJ exome AF: 0.0204

Gnomad EAS exome AF: 0.0000576

Gnomad FIN exome AF: 0.000322

Gnomad NFE exome AF: 0.00379

Gnomad OTH exome AF: 0.0206

GnomAD4 exome AF: 0.0108 AC: 15041 AN: 1393646 Hom.: 1296 Cov.: 29 AF XY: 0.0101 AC XY: 6887 AN XY: 683902

African (AFR) AF: 0.272 AC: 8645 AN: 31726

American (AMR) AF: 0.0214 AC: 829 AN: 38690

Ashkenazi Jewish (ASJ) AF: 0.0215 AC: 477 AN: 22180

East Asian (EAS) AF: 0.0000771 AC: 3 AN: 38892

South Asian (SAS) AF: 0.00756 AC: 570 AN: 75410

European-Finnish (FIN) AF: 0.000552 AC: 28 AN: 50734

Middle Eastern (MID) AF: 0.0591 AC: 322 AN: 5452

European-Non Finnish (NFE) AF: 0.00262 AC: 2815 AN: 1073190

Other (OTH) AF: 0.0236 AC: 1352 AN: 57372

GnomAD4 genome AF: 0.0771 AC: 11737 AN: 152214 Hom.: 1394 Cov.: 31 AF XY: 0.0747 AC XY: 5562 AN XY: 74442

African (AFR) AF: 0.258 AC: 10700 AN: 41500

American (AMR) AF: 0.0319 AC: 488 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.00622 AC: 30 AN: 4822

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10624

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.00381 AC: 259 AN: 68016

Other (OTH) AF: 0.0706 AC: 149 AN: 2110

Alfa AF: 0.0490 Hom.: 328

Bravo AF: 0.0862

Asia WGS AF: 0.0260 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.52
PhyloP100		-0.36
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: rs3842801; hg19: chr9-125154439;