Genetic Variant ENST00000608917.4:n.379G>C (chr1-186680486-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000608917.4(PACERR):n.379G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 473,838 control chromosomes in the GnomAD database, including 55 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 0.0099 ( 18 hom., cov: 32)

Exomes 𝑓: 0.012 ( 37 hom. )

Consequence

PACERR
ENST00000608917.4 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.92

Publications

7 publications found

Variant links:

Genes affected

PACERR (HGNC:50552): (PTGS2 antisense NFKB1 complex-mediated expression regulator RNA) This gene represents transcription of a long non-coding RNA produced in antisense to the prostaglandin-endoperoxide synthase 2 (PTGS2) gene. This transcript interacts with NF-kB transcriptional regulators to promote expression of PTGS2. [provided by RefSeq, Feb 2015]

PACERR links:

PTGS2 (HGNC:9605): (prostaglandin-endoperoxide synthase 2) Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase, is the key enzyme in prostaglandin biosynthesis, and acts both as a dioxygenase and as a peroxidase. There are two isozymes of PTGS: a constitutive PTGS1 and an inducible PTGS2, which differ in their regulation of expression and tissue distribution. This gene encodes the inducible isozyme. It is regulated by specific stimulatory events, suggesting that it is responsible for the prostanoid biosynthesis involved in inflammation and mitogenesis. [provided by RefSeq, Feb 2009]

PTGS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BS2

High Homozygotes in GnomAd4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS2	NM_000963.4 link	c.-196C>G		upstream_gene_variant		ENST00000367468.10	NP_000954.1
PACERR	NR_125801.1 link	n.-168G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGS2	ENST00000367468.10 link	c.-196C>G		upstream_gene_variant		1	NM_000963.4	ENSP00000356438.5

Frequencies

GnomAD3 genomes

AF:

0.00993

AC:

1511

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00436

Gnomad FIN

AF:

0.00773

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0139

Gnomad OTH

AF:

0.00960

GnomAD4 exome

AF:

0.0116

AC:

3721

AN:

321592

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

1933

AN XY:

169102

show subpopulations

African (AFR)

AF:

0.00197

AC:

AN:

7626

American (AMR)

AF:

0.00685

AC:

AN:

10212

Ashkenazi Jewish (ASJ)

AF:

0.0393

AC:

414

AN:

10532

East Asian (EAS)

AF:

0.00

AC:

AN:

23360

South Asian (SAS)

AF:

0.00547

AC:

138

AN:

25214

European-Finnish (FIN)

AF:

0.00995

AC:

252

AN:

25320

Middle Eastern (MID)

AF:

0.00539

AC:

AN:

1484

European-Non Finnish (NFE)

AF:

0.0131

AC:

2597

AN:

198376

Other (OTH)

AF:

0.0117

AC:

227

AN:

19468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

191

382

573

764

955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00993

AC:

1512

AN:

152246

Hom.:

Cov.:

AF XY:

0.00985

AC XY:

733

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00253

AC:

105

AN:

41550

American (AMR)

AF:

0.0142

AC:

218

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0343

AC:

119

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00458

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00773

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0139

AC:

944

AN:

68022

Other (OTH)

AF:

0.00950

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

156

233

311

389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00243

Hom.:

Bravo

AF:

0.00945

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

1.9

PromoterAI

0.027

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over