20-49561437-G-T

Variant names:

• chr20-49561437-G-T
• rs927068
• NM_000961.4:c.74+6606C>A

Variant summary

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

The NM_000961.4(PTGIS):​c.74+6606C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,038 control chromosomes in the GnomAD database, including 8,184 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 0.31 (8184 hom., cov: 32)
• Consequence: PTGIS NM_000961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGIS	NM_000961.4	c.74+6606C>A		intron_variant	Intron 1 of 9	ENST00000244043.5	NP_000952.1
PTGIS	XM_047440325.1	c.74+6606C>A		intron_variant	Intron 1 of 5		XP_047296281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGIS	ENST00000244043.5	c.74+6606C>A		intron_variant	Intron 1 of 9	1	NM_000961.4	ENSP00000244043.3
PTGIS	ENST00000478971.1	n.74+6606C>A		intron_variant	Intron 1 of 8	1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47388 AN: 151920 Hom.: 8149 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.312 AC: 47471 AN: 152038 Hom.: 8184 Cov.: 32 AF XY: 0.309 AC XY: 22979 AN XY: 74324

African (AFR) AF: 0.467 AC: 19366 AN: 41456

American (AMR) AF: 0.285 AC: 4350 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 712 AN: 3468

East Asian (EAS) AF: 0.188 AC: 972 AN: 5164

South Asian (SAS) AF: 0.205 AC: 985 AN: 4816

European-Finnish (FIN) AF: 0.274 AC: 2897 AN: 10570

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17164 AN: 67974

Other (OTH) AF: 0.304 AC: 641 AN: 2108

Alfa AF: 0.264 Hom.: 10594

Bravo AF: 0.321

Asia WGS AF: 0.218 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.7
DANN	Benign	0.71
PhyloP100		0.14
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: rs927068; hg19: chr20-48177974;