rs9920573

chr15-24543194-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000565295.6(PWRN1):n.1612-2869T>C variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.33

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PWRN1	ENST00000565295.6	n.1612-2869T>C		intron_variant, non_coding_transcript_variant		3
PWRN1	ENST00000568045.6	n.944+7388T>C		intron_variant, non_coding_transcript_variant		2
PWRN1	ENST00000651815.1	n.975-4136T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.407

Alfa AF: 0.413 Hom.: 2166

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9920573; hg19: chr15-24788341;