chr1-186681189-C-G

Variant names:

• chr1-186681189-C-G
• rs20417
• ENST00000608917.4:n.1082C>G

Variant summary

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

The NR_125801.1(PACERR):​n.536C>G 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 0.202 in 152,018 control chromosomes in the GnomAD database, including 3,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency:
  • Genomes: 𝑓 0.20 (3740 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: PACERR NR_125801.1 non_coding_transcript_exon
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: -3.13
• Publications: 483 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_125801.1. 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
	PACERR	NR_125801.1		n.536C>G		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PACERR	ENST00000608917.4	TSL:6	n.1082C>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30591 AN: 151892 Hom.: 3720 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0451

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0866

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 1 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.202 AC: 30652 AN: 152010 Hom.: 3740 Cov.: 32 AF XY: 0.197 AC XY: 14620 AN XY: 74322

African (AFR) AF: 0.334 AC: 13826 AN: 41420

American (AMR) AF: 0.181 AC: 2758 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3466

East Asian (EAS) AF: 0.0448 AC: 232 AN: 5174

South Asian (SAS) AF: 0.165 AC: 795 AN: 4826

European-Finnish (FIN) AF: 0.0866 AC: 919 AN: 10606

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.158 AC: 10728 AN: 67942

Other (OTH) AF: 0.210 AC: 444 AN: 2112

Alfa AF: 0.0650 Hom.: 82

Bravo AF: 0.214

Asia WGS AF: 0.155 AC: 541 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: other

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Cholangiocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.84
DANN	Benign	0.28
PhyloP100		-3.1
PromoterAI		0.074	Neutral
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs20417; hg19: chr1-186650321;