rs6478565

Variant names:

• chr9-122386353-A-G
• rs6478565
• NM_000962.4:c.1010-93A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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, AD, AR 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS1	NM_000962.4	MANE Select	c.1010-93A>G		intron	N/A	NP_000953.2
	PTGS1	NM_080591.3		c.1010-93A>G		intron	N/A	NP_542158.1	P23219-2
	PTGS1	NM_001271164.2		c.866-93A>G		intron	N/A	NP_001258093.1	A0A087X296

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS1	ENST00000362012.7	TSL:1 MANE Select	c.1010-93A>G		intron	N/A	ENSP00000354612.2	P23219-1
	PTGS1	ENST00000223423.8	TSL:1	c.1010-93A>G		intron	N/A	ENSP00000223423.4	P23219-2
	PTGS1	ENST00000863393.1		c.1064-93A>G		intron	N/A	ENSP00000533452.1

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

African (AFR) AF: 0.634 AC: 17790 AN: 28054

American (AMR) AF: 0.266 AC: 10196 AN: 38370

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 3277 AN: 20936

East Asian (EAS) AF: 0.0539 AC: 2062 AN: 38240

South Asian (SAS) AF: 0.206 AC: 14700 AN: 71378

European-Finnish (FIN) AF: 0.156 AC: 7613 AN: 48772

Middle Eastern (MID) AF: 0.189 AC: 927 AN: 4900

European-Non Finnish (NFE) AF: 0.164 AC: 150056 AN: 912558

Other (OTH) AF: 0.191 AC: 9869 AN: 51666

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

African (AFR) AF: 0.618 AC: 25629 AN: 41442

American (AMR) AF: 0.279 AC: 4273 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3472

East Asian (EAS) AF: 0.0675 AC: 349 AN: 5174

South Asian (SAS) AF: 0.197 AC: 952 AN: 4826

European-Finnish (FIN) AF: 0.151 AC: 1596 AN: 10576

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.176 AC: 11939 AN: 67962

Other (OTH) AF: 0.285 AC: 600 AN: 2104

Alfa AF: 0.206 Hom.: 17426

Bravo AF: 0.322

Asia WGS AF: 0.196 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.83
PhyloP100		0.069
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6478565; hg19: chr9-125148632;