15-24540053-G-A

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000565295.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PWRN1	ENST00000565295.6	TSL:3	n.1611+4247G>A		intron	N/A
	PWRN1	ENST00000568045.6	TSL:2	n.944+4247G>A		intron	N/A
	PWRN1	ENST00000651815.1		n.974+4247G>A		intron	N/A

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 v4.9

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;