Genetic Variant PRPF31:c.698-253C>T (chr19-54124246-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015629.4(PRPF31):c.698-253C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 633,210 control chromosomes in the GnomAD database, including 5,814 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 0.13 ( 1392 hom., cov: 32)

Exomes 𝑓: 0.13 ( 4422 hom. )

Consequence

PRPF31
NM_015629.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.509

Publications

7 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRPF31	NM_015629.4 link	c.698-253C>T	intron_variant	Intron 7 of 13	ENST00000321030.9	NP_056444.3	Q8WWY3-1
PRPF31	XM_006723137.5 link	c.698-253C>T	intron_variant	Intron 7 of 13		XP_006723200.1	Q8WWY3-1
PRPF31	XM_047438587.1 link	c.698-253C>T	intron_variant	Intron 7 of 9		XP_047294543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9 link	c.698-253C>T		intron_variant	Intron 7 of 13	1	NM_015629.4	ENSP00000324122.4		Q8WWY3-1

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20193

AN:

152070

Hom.:

1382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.0444

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.151

GnomAD4 exome

AF:

0.129

AC:

62022

AN:

481022

Hom.:

4422

Cov.:

AF XY:

0.130

AC XY:

32823

AN XY:

252606

show subpopulations

African (AFR)

AF:

0.132

AC:

1730

AN:

13062

American (AMR)

AF:

0.217

AC:

4141

AN:

19122

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

2091

AN:

13890

East Asian (EAS)

AF:

0.0303

AC:

949

AN:

31362

South Asian (SAS)

AF:

0.152

AC:

7086

AN:

46572

European-Finnish (FIN)

AF:

0.113

AC:

3368

AN:

29744

Middle Eastern (MID)

AF:

0.172

AC:

352

AN:

2042

European-Non Finnish (NFE)

AF:

0.129

AC:

38392

AN:

298174

Other (OTH)

AF:

0.145

AC:

3913

AN:

27054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

3048

6096

9144

12192

15240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.133

AC:

20228

AN:

152188

Hom.:

1392

Cov.:

AF XY:

0.132

AC XY:

9800

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.130

AC:

5407

AN:

41532

American (AMR)

AF:

0.193

AC:

2949

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

604

AN:

3468

East Asian (EAS)

AF:

0.0447

AC:

231

AN:

5166

South Asian (SAS)

AF:

0.136

AC:

658

AN:

4826

European-Finnish (FIN)

AF:

0.111

AC:

1174

AN:

10600

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.128

AC:

8731

AN:

68000

Other (OTH)

AF:

0.154

AC:

324

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

912

1823

2735

3646

4558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<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:

0.116

Hom.:

636

Bravo

AF:

0.139

Asia WGS

AF:

0.130

AC:

454

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

3.4

(source)

DANN

Benign

0.46

PhyloP100

0.51

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over