20-49513169-G-T

Variant names:

• chr20-49513169-G-T
• rs5629
• NM_000961.4:c.1117C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_000961.4(PTGIS):​c.1117C>A​(p.Arg373Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,613,868 control chromosomes in the GnomAD database, including 48,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.22 (3965 hom., cov: 31)
  • Exomes 𝑓: 0.24 (44655 hom.)
• Consequence: PTGIS NM_000961.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.45
• Publications: 47 publications found

Genes affected

PTGIS (HGNC:9603): (prostaglandin I2 synthase) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostglandin H2 to prostacyclin (prostaglandin I2), a potent vasodilator and inhibitor of platelet aggregation. An imbalance of prostacyclin and its physiological antagonist thromboxane A2 contribute to the development of myocardial infarction, stroke, and atherosclerosis. [provided by RefSeq, Jul 2008]

PTGIS Gene-Disease associations (from GenCC):

• essential hypertension, genetic

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 20-49513169-G-T is Benign according to our data. Variant chr20-49513169-G-T is described in ClinVar as Benign. ClinVar VariationId is 3060885.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.45 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000961.4. 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
	PTGIS	NM_000961.4	MANE Select	c.1117C>A	p.Arg373Arg	synonymous	Exon 8 of 10	NP_000952.1	Q16647

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGIS	ENST00000244043.5	TSL:1 MANE Select	c.1117C>A	p.Arg373Arg	synonymous	Exon 8 of 10	ENSP00000244043.3	Q16647
	PTGIS	ENST00000478971.1	TSL:1	n.938C>A		non_coding_transcript_exon	Exon 7 of 9
	PTGIS	ENST00000918261.1		c.814C>A	p.Arg272Arg	synonymous	Exon 6 of 8	ENSP00000588320.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33454 AN: 151912 Hom.: 3966 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.267

GnomAD2 exomes AF: 0.253 AC: 63525 AN: 251076 AF XY: 0.257

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.313

Gnomad ASJ exome AF: 0.343

Gnomad EAS exome AF: 0.220

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.248

Gnomad OTH exome AF: 0.274

GnomAD4 exome AF: 0.244 AC: 356948 AN: 1461836 Hom.: 44655 Cov.: 40 AF XY: 0.246 AC XY: 179006 AN XY: 727210

African (AFR) AF: 0.136 AC: 4561 AN: 33480

American (AMR) AF: 0.308 AC: 13753 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 9065 AN: 26134

East Asian (EAS) AF: 0.224 AC: 8874 AN: 39700

South Asian (SAS) AF: 0.285 AC: 24591 AN: 86258

European-Finnish (FIN) AF: 0.211 AC: 11279 AN: 53380

Middle Eastern (MID) AF: 0.364 AC: 2099 AN: 5768

European-Non Finnish (NFE) AF: 0.240 AC: 267012 AN: 1111998

Other (OTH) AF: 0.260 AC: 15714 AN: 60394

GnomAD4 genome AF: 0.220 AC: 33456 AN: 152032 Hom.: 3965 Cov.: 31 AF XY: 0.224 AC XY: 16668 AN XY: 74322

African (AFR) AF: 0.136 AC: 5623 AN: 41476

American (AMR) AF: 0.303 AC: 4625 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1135 AN: 3466

East Asian (EAS) AF: 0.227 AC: 1166 AN: 5140

South Asian (SAS) AF: 0.277 AC: 1332 AN: 4812

European-Finnish (FIN) AF: 0.215 AC: 2276 AN: 10582

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16505 AN: 67968

Other (OTH) AF: 0.265 AC: 559 AN: 2112

Alfa AF: 0.233 Hom.: 7826

Bravo AF: 0.221

Asia WGS AF: 0.250 AC: 866 AN: 3478

EpiCase AF: 0.263

EpiControl AF: 0.263

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PTGIS-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	12
DANN	Benign	0.66
PhyloP100		2.5
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: rs5629; hg19: chr20-48129706; COSMIC: COSV54837171;