Genetic Variant PRPF31:c.239-13C>T (chr19-54121847-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015629.4(PRPF31):c.239-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00412 in 1,604,744 control chromosomes in the GnomAD database, including 248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 126 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 122 hom. )

Consequence

PRPF31
NM_015629.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.476

Publications

0 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 19-54121847-C-T is Benign according to our data. Variant chr19-54121847-C-T is described in ClinVar as Benign. ClinVar VariationId is 330096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0747 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015629.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF31	NM_015629.4	MANE Select	c.239-13C>T		intron	N/A	NP_056444.3
	PRPF31-AS1	NR_186329.1		n.564G>A		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRPF31	ENST00000321030.9	TSL:1 MANE Select	c.239-13C>T	intron	N/A	ENSP00000324122.4	Q8WWY3-1
PRPF31	ENST00000951323.1		c.239-13C>T	intron	N/A	ENSP00000621382.1
PRPF31	ENST00000861422.1		c.332-13C>T	intron	N/A	ENSP00000531481.1

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3395

AN:

152224

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0771

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00975

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0177

GnomAD2 exomes

AF:

0.00572

AC:

1338

AN:

233922

AF XY:

0.00427

show subpopulations

Gnomad AFR exome

AF:

0.0808

Gnomad AMR exome

AF:

0.00388

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000171

Gnomad FIN exome

AF:

0.0000515

Gnomad NFE exome

AF:

0.000152

Gnomad OTH exome

AF:

0.00208

GnomAD4 exome

AF:

0.00221

AC:

3209

AN:

1452402

Hom.:

122

Cov.:

AF XY:

0.00191

AC XY:

1376

AN XY:

721674

show subpopulations

African (AFR)

AF:

0.0793

AC:

2642

AN:

33310

American (AMR)

AF:

0.00452

AC:

196

AN:

43362

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25912

East Asian (EAS)

AF:

0.0000763

AC:

AN:

39300

South Asian (SAS)

AF:

0.0000946

AC:

AN:

84604

European-Finnish (FIN)

AF:

0.0000191

AC:

AN:

52488

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000659

AC:

AN:

1107628

Other (OTH)

AF:

0.00455

AC:

273

AN:

60036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

177

354

531

708

885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<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:

0.0223

AC:

3397

AN:

152342

Hom.:

126

Cov.:

AF XY:

0.0219

AC XY:

1634

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0769

AC:

3198

AN:

41570

American (AMR)

AF:

0.00967

AC:

148

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68036

Other (OTH)

AF:

0.0175

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

171

342

512

683

854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0136

Hom.:

Bravo

AF:

0.0260

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.5

(source)

DANN

Benign

0.73

PhyloP100

0.48

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over