rs8030136

Positions:

• chr15-24777841-C-T

Variant summary

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

The ENST00000652025.1(PWRN1):​n.1488-29983C>T 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 0.125 in 152,156 control chromosomes in the GnomAD database, including 1,387 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 0.13 (1387 hom., cov: 32)
• Consequence: PWRN1 ENST00000652025.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PWRN1	ENST00000652025.1	n.1488-29983C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19049 AN: 152038 Hom.: 1384 Cov.: 32

Gnomad AFR AF: 0.0601

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0595

Gnomad SAS AF: 0.0881

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.125 AC: 19049 AN: 152156 Hom.: 1387 Cov.: 32 AF XY: 0.123 AC XY: 9114 AN XY: 74378

Gnomad4 AFR AF: 0.0600

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.0595

Gnomad4 SAS AF: 0.0882

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.133

Alfa AF: 0.141 Hom.: 215

Bravo AF: 0.129

Asia WGS AF: 0.0670 AC: 234 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.4
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8030136; hg19: chr15-25022988;