chr15-24326649-T-C

Variant names:

• chr15-24326649-T-C
• rs2016276
• ENST00000565295.6:n.425+190T>C

Variant summary

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

The ENST00000565295.6(PWRN1):​n.425+190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,016 control chromosomes in the GnomAD database, including 3,205 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 0.19 (3205 hom., cov: 32)
• Consequence: PWRN1 ENST00000565295.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 11 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]

ENSG00000293653 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105370733	XR_007064537.1	n.684+220T>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PWRN1	ENST00000565295.6	n.425+190T>C		intron_variant	Intron 2 of 14	3
PWRN1	ENST00000650870.1	n.165-113024T>C		intron_variant	Intron 2 of 5
PWRN1	ENST00000651552.2	n.1461+194T>C		intron_variant	Intron 9 of 18

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29318 AN: 151898 Hom.: 3206 Cov.: 32

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.193 AC: 29307 AN: 152016 Hom.: 3205 Cov.: 32 AF XY: 0.196 AC XY: 14572 AN XY: 74340

African (AFR) AF: 0.0927 AC: 3844 AN: 41466

American (AMR) AF: 0.194 AC: 2956 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3468

East Asian (EAS) AF: 0.429 AC: 2209 AN: 5154

South Asian (SAS) AF: 0.248 AC: 1192 AN: 4810

European-Finnish (FIN) AF: 0.237 AC: 2505 AN: 10582

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15209 AN: 67968

Other (OTH) AF: 0.197 AC: 415 AN: 2106

Alfa AF: 0.212 Hom.: 690

Bravo AF: 0.186

Asia WGS AF: 0.280 AC: 973 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.75
DANN	Benign	0.35
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs2016276; hg19: chr15-24571796; COSMIC: COSV52393777;