rs541873609

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000374199.9(PRPF4):c.-114_-97delTGTCAGTGACGCACTTCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,280,224 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

PRPF4
ENST00000374199.9 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts P:1U:2

Conservation

PhyloP100: 0.365

Publications

2 publications found

Variant links:

Genes affected

PRPF4 (HGNC:17349): (pre-mRNA splicing tri-snRNP complex factor PRPF4) The protein encoded by this gene is part of a heteromeric complex that binds U4, U5, and U6 small nuclear RNAs and is involved in pre-mRNA splicing. The encoded protein also is a mitotic checkpoint protein and a regulator of chemoresistance in human ovarian cancer. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2016]

PRPF4 links:

CDC26 (HGNC:17839): (cell division cycle 26) The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Cdc26, a component of cell cycle anaphase-promoting complex (APC). APC is composed of a group of highly conserved proteins and functions as a cell cycle-regulated ubiquitin-protein ligase. APC thus is responsible for the cell cycle regulated proteolysis of various proteins. [provided by RefSeq, Jul 2008]

CDC26 links:

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ACMG classification

Classification was made for transcript

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

BS2

High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF4	NM_001244926.2 link	c.-114_-97delTGTCAGTGACGCACTTCC		upstream_gene_variant		ENST00000374198.5	NP_001231855.1	O43172-2Q5T1M7
CDC26	NM_139286.4 link	c.-417_-400delGGAAGTGCGTCACTGACA		upstream_gene_variant		ENST00000374206.4	NP_644815.1	Q8NHZ8A0A024R832

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF4	ENST00000374198.5 link	c.-114_-97delTGTCAGTGACGCACTTCC		upstream_gene_variant		1	NM_001244926.2	ENSP00000363313.4		O43172-2
CDC26	ENST00000374206.4 link	c.-417_-400delGGAAGTGCGTCACTGACA		upstream_gene_variant		1	NM_139286.4	ENSP00000363322.3		Q8NHZ8

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000337

AC:

AN:

1127914

Hom.:

AF XY:

0.0000266

AC XY:

AN XY:

563130

show subpopulations

African (AFR)

AF:

0.0000797

AC:

AN:

25094

American (AMR)

AF:

0.0000633

AC:

AN:

31592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18708

East Asian (EAS)

AF:

0.000175

AC:

AN:

34246

South Asian (SAS)

AF:

0.0000148

AC:

AN:

67464

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4588

European-Non Finnish (NFE)

AF:

0.0000269

AC:

AN:

856226

Other (OTH)

AF:

0.0000831

AC:

AN:

48144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000105

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41572

American (AMR)

AF:

0.0000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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:

0.00

Hom.:

Bravo

AF:

0.0000529

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Retinitis pigmentosa 70

Pathogenic:1

Jun 01, 2014

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not specified

Uncertain:1

May 04, 2022

Mendelics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Uncertain:1

Dec 03, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant occurs in a non-coding region of the PRPF4 gene. It does not change the encoded amino acid sequence of the PRPF4 protein. This variant is present in population databases (rs541873609, gnomAD 0.1%). This variant has been observed in individual(s) with autosomal dominant retinitis pigmentosa (PMID: 24419317). This variant is also known as c.-114_-97del. Studies have shown that this variant alters PRPF4 gene expression (PMID: 24419317). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.36

Mutation Taster

=106/194

disease causing (ClinVar)

(source)

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over