rs975963

Positions:

• chr15-24772048-T-C

Variant summary

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

The ENST00000652025.1(PWRN1):​n.1488-35776T>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 0.65 in 152,094 control chromosomes in the GnomAD database, including 32,907 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 0.65 (32907 hom., cov: 33)
• Consequence: PWRN1 ENST00000652025.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.610

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 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	ENST00000652025.1	n.1488-35776T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98825 AN: 151976 Hom.: 32865 Cov.: 33

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.650 AC: 98923 AN: 152094 Hom.: 32907 Cov.: 33 AF XY: 0.650 AC XY: 48291 AN XY: 74308

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.686

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.651

Alfa AF: 0.610 Hom.: 3558

Bravo AF: 0.661

Asia WGS AF: 0.700 AC: 2430 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.7
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs975963; hg19: chr15-25017195;