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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014502.5. 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
	PRPF19	NM_014502.5	MANE Select	c.828+147T>C		intron	N/A	NP_055317.1	Q9UMS4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRPF19	ENST00000227524.9	TSL:1 MANE Select	c.828+147T>C	intron	N/A	ENSP00000227524.4	Q9UMS4
PRPF19	ENST00000907533.1		c.834+147T>C	intron	N/A	ENSP00000577592.1
PRPF19	ENST00000918252.1		c.825+147T>C	intron	N/A	ENSP00000588311.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over