rs7928208

Positions:

• chr11-60900435-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PRPF19	NM_014502.5	c.828+147T>C		intron_variant		ENST00000227524.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF19	ENST00000227524.9	c.828+147T>C		intron_variant		1	NM_014502.5	P1
PRPF19	ENST00000540473.5	c.114+875T>C		intron_variant		5
PRPF19	ENST00000541371.5	c.718+419T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49229 AN: 151978 Hom.: 9009 Cov.: 32

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

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.419

Gnomad4 EAS exome AF: 0.327

Gnomad4 SAS exome AF: 0.413

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.392

Gnomad4 OTH exome AF: 0.373

GnomAD4 genome AF: 0.324 AC: 49260 AN: 152098 Hom.: 9013 Cov.: 32 AF XY: 0.328 AC XY: 24405 AN XY: 74352

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.352

Alfa AF: 0.347 Hom.: 1988

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
DANN	Benign	0.65

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

LitVar

Other links and lift over

dbSNP: rs7928208; hg19: chr11-60667907; COSMIC: COSV57129715; COSMIC: COSV57129715;