dbSNP rs59977379: PRPF31:c.322+142A>G (chr19-54122085-A-G) – 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.322+142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 901,110 control chromosomes in the GnomAD database, including 1,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.052 ( 225 hom., cov: 32)

Exomes 𝑓: 0.056 ( 1355 hom. )

Consequence

PRPF31
NM_015629.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.367

Publications

2 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=-0.94).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0605 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.322+142A>G		intron	N/A	NP_056444.3
	PRPF31-AS1	NR_186329.1		n.473T>C		non_coding_transcript_exon	Exon 2 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRPF31	ENST00000321030.9	TSL:1 MANE Select	c.322+142A>G	intron	N/A	ENSP00000324122.4	Q8WWY3-1
PRPF31	ENST00000951323.1		c.322+142A>G	intron	N/A	ENSP00000621382.1
PRPF31	ENST00000861422.1		c.415+142A>G	intron	N/A	ENSP00000531481.1

Frequencies

GnomAD3 genomes

AF:

0.0521

AC:

7929

AN:

152128

Hom.:

223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0399

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.0373

Gnomad ASJ

AF:

0.0752

Gnomad EAS

AF:

0.0100

Gnomad SAS

AF:

0.0439

Gnomad FIN

AF:

0.0772

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0620

Gnomad OTH

AF:

0.0373

GnomAD4 exome

AF:

0.0564

AC:

42263

AN:

748864

Hom.:

1355

Cov.:

AF XY:

0.0562

AC XY:

21910

AN XY:

389716

show subpopulations

African (AFR)

AF:

0.0413

AC:

802

AN:

19408

American (AMR)

AF:

0.0264

AC:

915

AN:

34636

Ashkenazi Jewish (ASJ)

AF:

0.0713

AC:

1490

AN:

20892

East Asian (EAS)

AF:

0.0120

AC:

393

AN:

32736

South Asian (SAS)

AF:

0.0457

AC:

3026

AN:

66166

European-Finnish (FIN)

AF:

0.0733

AC:

2487

AN:

33952

Middle Eastern (MID)

AF:

0.0289

AC:

107

AN:

3704

European-Non Finnish (NFE)

AF:

0.0622

AC:

31116

AN:

500372

Other (OTH)

AF:

0.0521

AC:

1927

AN:

36998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

2345

4690

7035

9380

11725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

716

1432

2148

2864

3580

<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:

0.0522

AC:

7941

AN:

152246

Hom.:

225

Cov.:

AF XY:

0.0521

AC XY:

3874

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0400

AC:

1664

AN:

41562

American (AMR)

AF:

0.0373

AC:

570

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0752

AC:

261

AN:

3470

East Asian (EAS)

AF:

0.0102

AC:

AN:

5172

South Asian (SAS)

AF:

0.0438

AC:

211

AN:

4822

European-Finnish (FIN)

AF:

0.0772

AC:

818

AN:

10594

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0620

AC:

4221

AN:

68026

Other (OTH)

AF:

0.0369

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

402

803

1205

1606

2008

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0595

Hom.:

Bravo

AF:

0.0477

Asia WGS

AF:

0.0300

AC:

107

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.71

(source)

DANN

Benign

0.26

PhyloP100

-0.37

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over