rs6576326

Variant names:

• chr15-24540053-G-A
• rs6576326
• ENST00000565295.6:n.1611+4247G>A

Variant summary

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

The ENST00000565295.6(PWRN1):​n.1611+4247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,004 control chromosomes in the GnomAD database, including 13,847 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 (13847 hom., cov: 33)
• Consequence: PWRN1 ENST00000565295.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958
• Publications: 9 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]

LOC105370733 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105370733	XR_007064536.1	n.1679-1527G>A		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PWRN1	ENST00000565295.6	n.1611+4247G>A		intron_variant	Intron 9 of 14	3
PWRN1	ENST00000568045.6	n.944+4247G>A		intron_variant	Intron 6 of 12	2
PWRN1	ENST00000651815.1	n.974+4247G>A		intron_variant	Intron 7 of 8

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64661 AN: 151886 Hom.: 13841 Cov.: 33

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.426 AC: 64686 AN: 152004 Hom.: 13847 Cov.: 33 AF XY: 0.423 AC XY: 31436 AN XY: 74286

African (AFR) AF: 0.470 AC: 19467 AN: 41450

American (AMR) AF: 0.396 AC: 6046 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1186 AN: 3470

East Asian (EAS) AF: 0.324 AC: 1666 AN: 5136

South Asian (SAS) AF: 0.422 AC: 2036 AN: 4824

European-Finnish (FIN) AF: 0.418 AC: 4413 AN: 10560

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

European-Non Finnish (NFE) AF: 0.418 AC: 28387 AN: 67974

Other (OTH) AF: 0.408 AC: 861 AN: 2112

Alfa AF: 0.415 Hom.: 42081

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	-1.0
CADD	Benign	3.0
DANN	Benign	0.18
PhyloP100		-0.96

Splicing

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

Other links and lift over

dbSNP: rs6576326; hg19: chr15-24785200;