rs35600665

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 ENST00000565512.6(PWRN1):​n.111-12717C>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 ENST00000565512.6 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000565512.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PWRN1	ENST00000562244.2	TSL:3	n.756+2816C>T		intron	N/A
	PWRN1	ENST00000565295.6	TSL:3	n.667+4517C>T		intron	N/A
	PWRN1	ENST00000565512.6	TSL:2	n.111-12717C>T		intron	N/A

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs35600665;

hg19: chr15-24741291;