rs4836885

chr9-122384090-T-C

Variant summary

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

The NM_000962.4(PTGS1):c.1009+335T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,026 control chromosomes in the GnomAD database, including 7,340 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 0.25 (7340 hom., cov: 31)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGS1	NM_000962.4	c.1009+335T>C		intron_variant		ENST00000362012.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGS1	ENST00000362012.7	c.1009+335T>C		intron_variant		1	NM_000962.4	P1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38106 AN: 151908 Hom.: 7302 Cov.: 31

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0446

Gnomad SAS AF: 0.0842

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.251 AC: 38192 AN: 152026 Hom.: 7340 Cov.: 31 AF XY: 0.247 AC XY: 18346 AN XY: 74306

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0447

Gnomad4 SAS AF: 0.0834

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.236

Alfa AF: 0.172 Hom.: 1475

Bravo AF: 0.272

Asia WGS AF: 0.110 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.10
Dann	Benign	0.28

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: rs4836885; hg19: chr9-125146369;