rs11587682

Variant names:

• chr1-150351808-C-T
• rs11587682
• NM_004698.4:c.1906-1025C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004698.4(PRPF3):​c.1906-1025C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0819 in 151,746 control chromosomes in the GnomAD database, including 677 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 0.082 (677 hom., cov: 30)
• Consequence: PRPF3 NM_004698.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708
• Publications: 20 publications found

Genes affected

PRPF3 (HGNC:17348): (pre-mRNA processing factor 3) The removal of introns from nuclear pre-mRNAs occurs on complexes called spliceosomes, which are made up of 4 small nuclear ribonucleoprotein (snRNP) particles and an undefined number of transiently associated splicing factors. This gene product is one of several proteins that associate with U4 and U6 snRNPs. Mutations in this gene are associated with retinitis pigmentosa-18. [provided by RefSeq, Jul 2008]

PRPF3 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 18

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF3	NM_004698.4	c.1906-1025C>T		intron_variant	Intron 15 of 15	ENST00000324862.7	NP_004689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF3	ENST00000324862.7	c.1906-1025C>T		intron_variant	Intron 15 of 15	1	NM_004698.4	ENSP00000315379.6
PRPF3	ENST00000467329.5	n.2233-1025C>T		intron_variant	Intron 12 of 12	5
PRPF3	ENST00000470824.1	n.536-1025C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12430 AN: 151626 Hom.: 677 Cov.: 30

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0293

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0677

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0819 AC: 12426 AN: 151746 Hom.: 677 Cov.: 30 AF XY: 0.0811 AC XY: 6008 AN XY: 74100

African (AFR) AF: 0.0208 AC: 860 AN: 41402

American (AMR) AF: 0.0674 AC: 1023 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 335 AN: 3462

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.0297 AC: 143 AN: 4808

European-Finnish (FIN) AF: 0.155 AC: 1623 AN: 10468

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8215 AN: 67934

Other (OTH) AF: 0.0670 AC: 141 AN: 2106

Alfa AF: 0.103 Hom.: 2219

Bravo AF: 0.0725

Asia WGS AF: 0.0180 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.52
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11587682; hg19: chr1-150324284;