rs1058572

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_015629.4(PRPF31):c.564G>A(p.Glu188Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0266 in 1,611,796 control chromosomes in the GnomAD database, including 695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 58 hom., cov: 33)

Exomes 𝑓: 0.027 ( 637 hom. )

Consequence

PRPF31
NM_015629.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.15

Publications

8 publications found

Variant links:

Genes affected

PRPF31 (HGNC:15446): (pre-mRNA processing factor 31) This gene encodes a component of the spliceosome complex and is one of several retinitis pigmentosa-causing genes. When the gene product is added to the spliceosome complex, activation occurs.[provided by RefSeq, Jan 2009]

PRPF31 links:

PRPF31-AS1 (HGNC:40700): (PRPF31 antisense RNA 1)

PRPF31-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 19-54123785-G-A is Benign according to our data. Variant chr19-54123785-G-A is described in ClinVar as Benign. ClinVar VariationId is 330098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0221 (3369/152304) while in subpopulation NFE AF = 0.0323 (2198/68022). AF 95% confidence interval is 0.0312. There are 58 homozygotes in GnomAd4. There are 1644 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 3369 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF31	NM_015629.4 link	c.564G>A	p.Glu188Glu	synonymous_variant	Exon 7 of 14	ENST00000321030.9	NP_056444.3	Q8WWY3-1
PRPF31	XM_006723137.5 link	c.564G>A	p.Glu188Glu	synonymous_variant	Exon 7 of 14		XP_006723200.1	Q8WWY3-1
PRPF31	XM_047438587.1 link	c.564G>A	p.Glu188Glu	synonymous_variant	Exon 7 of 10		XP_047294543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9 link	c.564G>A	p.Glu188Glu	synonymous_variant	Exon 7 of 14	1	NM_015629.4	ENSP00000324122.4		Q8WWY3-1

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3367

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00521

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0144

Gnomad ASJ

AF:

0.0207

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.0530

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0323

Gnomad OTH

AF:

0.0158

GnomAD2 exomes

AF:

0.0226

AC:

5608

AN:

248026

AF XY:

0.0222

show subpopulations

Gnomad AFR exome

AF:

0.00484

Gnomad AMR exome

AF:

0.0106

Gnomad ASJ exome

AF:

0.0199

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0557

Gnomad NFE exome

AF:

0.0320

Gnomad OTH exome

AF:

0.0227

GnomAD4 exome

AF:

0.0271

AC:

39575

AN:

1459492

Hom.:

637

Cov.:

AF XY:

0.0263

AC XY:

19092

AN XY:

726196

show subpopulations

African (AFR)

AF:

0.00442

AC:

148

AN:

33478

American (AMR)

AF:

0.0107

AC:

476

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

513

AN:

26132

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39694

South Asian (SAS)

AF:

0.00422

AC:

364

AN:

86244

European-Finnish (FIN)

AF:

0.0515

AC:

2645

AN:

51348

Middle Eastern (MID)

AF:

0.00295

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0307

AC:

34110

AN:

1111814

Other (OTH)

AF:

0.0215

AC:

1299

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

2487

4975

7462

9950

12437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1252

2504

3756

5008

6260

<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:

0.0221

AC:

3369

AN:

152304

Hom.:

Cov.:

AF XY:

0.0221

AC XY:

1644

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00520

AC:

216

AN:

41570

American (AMR)

AF:

0.0144

AC:

221

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0207

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0530

AC:

562

AN:

10604

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0323

AC:

2198

AN:

68022

Other (OTH)

AF:

0.0156

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

176

351

527

702

878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0277

Hom.:

193

Bravo

AF:

0.0183

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0293

EpiControl

AF:

0.0280

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Retinitis pigmentosa

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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