dbSNP rs7928208: PRPF19:c.828+147T>C (chr11-60900435-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_014502.5(PRPF19):c.828+147T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 648,438 control chromosomes in the GnomAD database, including 46,373 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 0.32 ( 9013 hom., cov: 32)

Exomes 𝑓: 0.38 ( 37360 hom. )

Consequence

PRPF19
NM_014502.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.280

Publications

12 publications found

Variant links:

Genes affected

PRPF19 (HGNC:17896): (pre-mRNA processing factor 19) Enables identical protein binding activity and ubiquitin-ubiquitin ligase activity. Involved in several processes, including DNA damage checkpoint signaling; cellular protein metabolic process; and mRNA splicing, via spliceosome. Acts upstream of or within protein polyubiquitination. Located in cytoplasm; nuclear speck; and site of double-strand break. Part of Prp19 complex and U2-type catalytic step 2 spliceosome. Colocalizes with DNA replication factor A complex. [provided by Alliance of Genome Resources, Apr 2022]

PRPF19 Gene-Disease associations (from GenCC):

PRPF19-related neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: G2P

PRPF19 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=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF19	NM_014502.5 link	c.828+147T>C		intron_variant	Intron 10 of 15	ENST00000227524.9	NP_055317.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRPF19	ENST00000227524.9 link	c.828+147T>C	intron_variant	Intron 10 of 15	1	NM_014502.5	ENSP00000227524.4	Q9UMS4
PRPF19	ENST00000541371.5 link	c.718+419T>C	intron_variant	Intron 9 of 9	3		ENSP00000440266.1	F5GY56
PRPF19	ENST00000540473.5 link	c.114+875T>C	intron_variant	Intron 3 of 3	5		ENSP00000443031.1	H0YGF3

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

49229

AN:

151978

Hom.:

9009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.398

Gnomad ASJ

AF:

0.418

Gnomad EAS

AF:

0.303

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.351

GnomAD4 exome

AF:

0.384

AC:

190513

AN:

496340

Hom.:

37360

AF XY:

0.385

AC XY:

99953

AN XY:

259380

show subpopulations

African (AFR)

AF:

0.141

AC:

1831

AN:

13014

American (AMR)

AF:

0.413

AC:

7886

AN:

19092

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

5834

AN:

13908

East Asian (EAS)

AF:

0.327

AC:

10225

AN:

31306

South Asian (SAS)

AF:

0.413

AC:

19044

AN:

46096

European-Finnish (FIN)

AF:

0.395

AC:

17672

AN:

44684

Middle Eastern (MID)

AF:

0.392

AC:

804

AN:

2050

European-Non Finnish (NFE)

AF:

0.392

AC:

117065

AN:

298990

Other (OTH)

AF:

0.373

AC:

10152

AN:

27200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

5880

11760

17640

23520

29400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

978

1956

2934

3912

4890

<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:

0.324

AC:

49260

AN:

152098

Hom.:

9013

Cov.:

AF XY:

0.328

AC XY:

24405

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.146

AC:

6069

AN:

41522

American (AMR)

AF:

0.399

AC:

6091

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.418

AC:

1449

AN:

3464

East Asian (EAS)

AF:

0.304

AC:

1573

AN:

5180

South Asian (SAS)

AF:

0.399

AC:

1924

AN:

4822

European-Finnish (FIN)

AF:

0.400

AC:

4219

AN:

10550

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.394

AC:

26760

AN:

67968

Other (OTH)

AF:

0.352

AC:

742

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1618

3236

4854

6472

8090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

500

1000

1500

2000

2500

<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:

0.342

Hom.:

1997

Bravo

AF:

0.315

Asia WGS

AF:

0.330

AC:

1149

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.15

(source)

DANN

Benign

0.65

PhyloP100

-0.28

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