dbSNP rs2001867: LOC105370733:n.24261346G>C (chr15-24261346-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The variant allele was found at a frequency of 0.000767 in 131,678 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00077 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LOC105370733
intragenic

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.29

Publications

1 publications found

Variant links:

Genes affected

LOC105370733 (HGNC:):

LOC105370733 links:

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105370733		n.24261346G>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
PWRN1	ENST00000561964.1 link	n.223+4089G>C	intron_variant	Intron 2 of 2	5
PWRN1	ENST00000565295.6 link	n.138-64826G>C	intron_variant	Intron 1 of 14	3
PWRN1	ENST00000566676.1 link	n.54+14G>C	intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.000737

AC:

AN:

131572

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00173

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000294

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00355

Gnomad NFE

AF:

0.000148

Gnomad OTH

AF:

0.00112

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:

0.000767

AC:

101

AN:

131678

Hom.:

Cov.:

AF XY:

0.000676

AC XY:

AN XY:

63582

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00183

AC:

AN:

37756

American (AMR)

AF:

0.00151

AC:

AN:

12554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3098

East Asian (EAS)

AF:

0.00

AC:

AN:

2924

South Asian (SAS)

AF:

0.000295

AC:

AN:

3390

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8500

Middle Eastern (MID)

AF:

0.00376

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.000148

AC:

AN:

60614

Other (OTH)

AF:

0.00111

AC:

AN:

1804

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.357

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000674

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.7

(source)

DANN

Benign

0.17

PhyloP100

-1.3

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