NM_000962.4:c.1009+345G>A

Variant names:

• chr9-122384100-G-A
• rs10306230
• NM_000962.4:c.1009+345G>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.1009+345G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 152,132 control chromosomes in the GnomAD database, including 97 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 0.034 (97 hom., cov: 31)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS1	NM_000962.4	c.1009+345G>A		intron_variant	Intron 8 of 10	ENST00000362012.7	NP_000953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGS1	ENST00000362012.7	c.1009+345G>A		intron_variant	Intron 8 of 10	1	NM_000962.4	ENSP00000354612.2

Frequencies

GnomAD3 genomes AF: 0.0339 AC: 5157 AN: 152014 Hom.: 96 Cov.: 31

Gnomad AFR AF: 0.0563

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.0358

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0340 AC: 5167 AN: 152132 Hom.: 97 Cov.: 31 AF XY: 0.0331 AC XY: 2462 AN XY: 74372

African (AFR) AF: 0.0564 AC: 2340 AN: 41498

American (AMR) AF: 0.0181 AC: 277 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0311 AC: 108 AN: 3472

East Asian (EAS) AF: 0.0356 AC: 184 AN: 5162

South Asian (SAS) AF: 0.0303 AC: 146 AN: 4822

European-Finnish (FIN) AF: 0.0258 AC: 274 AN: 10608

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.0248 AC: 1683 AN: 67980

Other (OTH) AF: 0.0327 AC: 69 AN: 2110

Alfa AF: 0.0281 Hom.: 99

Bravo AF: 0.0338

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.80
PhyloP100		-0.54
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: rs10306230; hg19: chr9-125146379;