rs9920573

Variant names:

• chr15-24543194-T-C
• rs9920573
• ENST00000565295.6:n.1612-2869T>C

Variant summary

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

The ENST00000565295.6(PWRN1):​n.1612-2869T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,952 control chromosomes in the GnomAD database, including 13,816 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 0.43 (13816 hom., cov: 32)
• Consequence: PWRN1 ENST00000565295.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.33
• Publications: 0 publications found

Genes affected

PWRN1 (HGNC:33235): (Prader-Willi region non-protein coding RNA 1) This gene is located in the Prader-Willi syndrome (PWS) region of chromosome 15, which is known to undergo imprinting. The transcript is believed to be non-coding. It is bi-allelically expressed in testis and kidney, but mono-allelically expressed from the paternal allele in brain. This gene is poly-adenylated and is known to undergo alternative splicing. Transcript variants may represent part of a complex imprinting center-SNURF-SNRPN transcription unit. The contribution of this gene to the PWS phenotype is unknown, but it has been suggested that it may play a role in establishing paternal imprinting in the PWS region, perhaps by maintaining the paternal allele in an open chromatin configuration. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PWRN1	ENST00000565295.6	n.1612-2869T>C		intron_variant	Intron 9 of 14	3
PWRN1	ENST00000568045.6	n.944+7388T>C		intron_variant	Intron 6 of 12	2
PWRN1	ENST00000651815.1	n.975-4136T>C		intron_variant	Intron 7 of 8

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64570 AN: 151834 Hom.: 13808 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.425 AC: 64597 AN: 151952 Hom.: 13816 Cov.: 32 AF XY: 0.422 AC XY: 31370 AN XY: 74264

African (AFR) AF: 0.469 AC: 19416 AN: 41412

American (AMR) AF: 0.396 AC: 6047 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1187 AN: 3470

East Asian (EAS) AF: 0.324 AC: 1669 AN: 5146

South Asian (SAS) AF: 0.422 AC: 2038 AN: 4824

European-Finnish (FIN) AF: 0.415 AC: 4390 AN: 10568

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28366 AN: 67948

Other (OTH) AF: 0.407 AC: 858 AN: 2108

Alfa AF: 0.414 Hom.: 2253

Bravo AF: 0.426

Asia WGS AF: 0.391 AC: 1361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.28
DANN	Benign	0.042
PhyloP100		-3.3

Splicing

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

Other links and lift over

dbSNP: rs9920573; hg19: chr15-24788341;