ENST00000562244.2:n.756+2816C>T

Variant names:

• chr15-24496144-C-T
• rs35600665
• ENST00000562244.2:n.756+2816C>T

Variant summary

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

The ENST00000562244.2(PWRN1):​n.756+2816C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 151,910 control chromosomes in the GnomAD database, including 3,934 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 0.20 (3934 hom., cov: 33)
• Consequence: PWRN1 ENST00000562244.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105370733	XR_007064536.1	n.1036+4517C>T		intron_variant	Intron 2 of 6
LOC105370733	XR_007064537.1	n.795-12717C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PWRN1	ENST00000562244.2	n.756+2816C>T		intron_variant	Intron 6 of 11	3
PWRN1	ENST00000565295.6	n.667+4517C>T		intron_variant	Intron 3 of 14	3
PWRN1	ENST00000565512.6	n.111-12717C>T		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31092 AN: 151792 Hom.: 3932 Cov.: 33

Gnomad AFR AF: 0.0919

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.205 AC: 31092 AN: 151910 Hom.: 3934 Cov.: 33 AF XY: 0.204 AC XY: 15153 AN XY: 74252

African (AFR) AF: 0.0919 AC: 3808 AN: 41454

American (AMR) AF: 0.189 AC: 2886 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3462

East Asian (EAS) AF: 0.152 AC: 781 AN: 5148

South Asian (SAS) AF: 0.185 AC: 892 AN: 4826

European-Finnish (FIN) AF: 0.277 AC: 2923 AN: 10544

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18474 AN: 67902

Other (OTH) AF: 0.203 AC: 428 AN: 2108

Alfa AF: 0.233 Hom.: 3161

Bravo AF: 0.193

Asia WGS AF: 0.183 AC: 634 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.38
DANN	Benign	0.53
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs35600665; hg19: chr15-24741291;