Genetic Variant PWRN4:n.784+24783T>C (chr15-24003994-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000652183.1(PWRN4):n.784+24783T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,768 control chromosomes in the GnomAD database, including 8,186 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 0.32 ( 8186 hom., cov: 32)

Consequence

PWRN4
ENST00000652183.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.86

Publications

2 publications found

Variant links:

Genes affected

PWRN4 (HGNC:49130): (Prader-Willi region non-protein coding RNA 4)

PWRN4 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=-1.0).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PWRN4	NR_126392.1 link	n.445+559T>C		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
PWRN4	ENST00000652183.1 link	n.784+24783T>C	intron_variant	Intron 7 of 10
PWRN4	ENST00000661343.1 link	n.487+24783T>C	intron_variant	Intron 5 of 8
PWRN4	ENST00000663707.1 link	n.435+24783T>C	intron_variant	Intron 4 of 6

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49262

AN:

151652

Hom.:

8168

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.282

Gnomad EAS

AF:

0.170

Gnomad SAS

AF:

0.286

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.305

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

GnomAD4 genome

AF:

0.325

AC:

49306

AN:

151768

Hom.:

8186

Cov.:

AF XY:

0.318

AC XY:

23577

AN XY:

74146

show subpopulations

African (AFR)

AF:

0.339

AC:

14038

AN:

41402

American (AMR)

AF:

0.270

AC:

4104

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

980

AN:

3470

East Asian (EAS)

AF:

0.169

AC:

870

AN:

5134

South Asian (SAS)

AF:

0.284

AC:

1366

AN:

4806

European-Finnish (FIN)

AF:

0.270

AC:

2840

AN:

10516

Middle Eastern (MID)

AF:

0.264

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.356

AC:

24185

AN:

67902

Other (OTH)

AF:

0.301

AC:

635

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1700

3400

5099

6799

8499

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<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:

0.342

Hom.:

4725

Bravo

AF:

0.324

Asia WGS

AF:

0.237

AC:

824

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.47

(source)

DANN

Benign

0.38

PhyloP100

-2.9

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