1-186680486-G-A

Variant names:

• chr1-186680486-G-A
• rs20424
• ENST00000608917.4:n.379G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000608917.4(PACERR):​n.379G>A 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 0.00000311 in 321,634 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: PACERR ENST00000608917.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 7 publications found

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000608917.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	NM_000963.4	MANE Select	c.-196C>T		upstream_gene	N/A	NP_000954.1
	PACERR	NR_125801.1		n.-168G>A		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PACERR	ENST00000608917.4	TSL:6	n.379G>A		non_coding_transcript_exon	Exon 1 of 1
	PTGS2	ENST00000680451.1		c.-113-83C>T		intron	N/A	ENSP00000506242.1
	PTGS2	ENST00000367468.10	TSL:1 MANE Select	c.-196C>T		upstream_gene	N/A	ENSP00000356438.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000311 AC: 1 AN: 321634 Hom.: 0 Cov.: 4 AF XY: 0.00000591 AC XY: 1 AN XY: 169126

African (AFR) AF: 0.00 AC: 0 AN: 7626

American (AMR) AF: 0.00 AC: 0 AN: 10214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10534

East Asian (EAS) AF: 0.00 AC: 0 AN: 23360

South Asian (SAS) AF: 0.00 AC: 0 AN: 25220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25324

Middle Eastern (MID) AF: 0.000674 AC: 1 AN: 1484

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 198400

Other (OTH) AF: 0.00 AC: 0 AN: 19472

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Benign	0.85
PhyloP100		1.9
PromoterAI		-0.090	Neutral

Splicing

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

Other links and lift over

dbSNP: rs20424; hg19: chr1-186649618;