15-24724313-A-G

Variant names:

• chr15-24724313-A-G
• rs10519471
• ENST00000650707.1:n.408-83511A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000650707.1(ENSG00000286110):​n.408-83511A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0346 in 152,260 control chromosomes in the GnomAD database, including 93 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 0.035 (93 hom., cov: 32)
• Consequence: ENSG00000286110 ENST00000650707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

Genes affected

ENSG00000286110 (HGNC:):

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=-0.96).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0346 (5262/152260) while in subpopulation AFR AF= 0.0481 (2000/41554). AF 95% confidence interval is 0.0464. There are 93 homozygotes in gnomad4. There are 2508 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 93 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286110	ENST00000650707.1	n.408-83511A>G		intron_variant	Intron 3 of 6
ENSG00000286110	ENST00000651136.1	n.1531-83511A>G		intron_variant	Intron 9 of 14
PWRN1	ENST00000652025.1	n.1488-83511A>G		intron_variant	Intron 10 of 13

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5262 AN: 152142 Hom.: 93 Cov.: 32

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.0239

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0293

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0341

Gnomad OTH AF: 0.0320

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

GnomAD4 genome AF: 0.0346 AC: 5262 AN: 152260 Hom.: 93 Cov.: 32 AF XY: 0.0337 AC XY: 2508 AN XY: 74444

Gnomad4 AFR AF: 0.0481

Gnomad4 AMR AF: 0.0239

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0291

Gnomad4 FIN AF: 0.0291

Gnomad4 NFE AF: 0.0341

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0132 Hom.: 6

Bravo AF: 0.0350

Asia WGS AF: 0.0140 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.063
DANN	Benign	0.90

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10519471; hg19: chr15-24969460;