dbSNP rs1846338: PWRN1:n.402G>A (chr15-24225587-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000568541.1(PWRN1):n.402G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 152,018 control chromosomes in the GnomAD database, including 156 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 0.024 ( 156 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PWRN1
ENST00000568541.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.212

Publications

0 publications found

Variant links:

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]

PWRN1 links:

LOC105370733 (HGNC:):

LOC105370733 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105370733		n.24225587G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
PWRN1	ENST00000568541.1 link	n.402G>A	non_coding_transcript_exon_variant	Exon 2 of 3	2
PWRN1	ENST00000565295.6 link	n.137+80088G>A	intron_variant	Intron 1 of 14	3
PWRN1	ENST00000570105.2 link	n.41-154G>A	intron_variant	Intron 1 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.0235

AC:

3568

AN:

151898

Hom.:

154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0818

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00651

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000625

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.0143

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0236

AC:

3585

AN:

152018

Hom.:

156

Cov.:

AF XY:

0.0233

AC XY:

1734

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.0820

AC:

3398

AN:

41460

American (AMR)

AF:

0.00650

AC:

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5152

South Asian (SAS)

AF:

0.000625

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000500

AC:

AN:

67986

Other (OTH)

AF:

0.0147

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

181

363

544

726

907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00808

Hom.:

Bravo

AF:

0.0274

Asia WGS

AF:

0.00549

AC:

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.1

(source)

DANN

Benign

0.28

PhyloP100

0.21

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over