Variant rs11078563 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006445.4(PRPF8):c.3774+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,613,478 control chromosomes in the GnomAD database, including 44,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 9076 hom., cov: 32)

Exomes 𝑓: 0.21 ( 35281 hom. )

Consequence

PRPF8
NM_006445.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.00009967

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0630

Variant links:

Genes affected

PRPF8 (HGNC:17340): (pre-mRNA processing factor 8) Pre-mRNA splicing occurs in 2 sequential transesterification steps. The protein encoded by this gene is a component of both U2- and U12-dependent spliceosomes, and found to be essential for the catalytic step II in pre-mRNA splicing process. It contains several WD repeats, which function in protein-protein interactions. This protein has a sequence similarity to yeast Prp8 protein. This gene is a candidate gene for autosomal dominant retinitis pigmentosa. [provided by RefSeq, Jul 2008]

PRPF8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 17-1673075-C-T is Benign according to our data. Variant chr17-1673075-C-T is described in ClinVar as [Benign]. Clinvar id is 321889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRPF8	NM_006445.4 linkuse as main transcript	c.3774+6G>A		splice_donor_region_variant, intron_variant		ENST00000304992.11
PRPF8	XM_024450537.2 linkuse as main transcript	c.3774+6G>A		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF8	ENST00000304992.11 linkuse as main transcript	c.3774+6G>A		splice_donor_region_variant, intron_variant		1	NM_006445.4	P1

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45389

AN:

151990

Hom.:

9035

Cov.:

show subpopulations

Gnomad AFR

AF:

0.568

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.0691

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.267

GnomAD3 exomes

AF:

0.207

AC:

52000

AN:

251082

Hom.:

7021

AF XY:

0.202

AC XY:

27450

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.573

Gnomad AMR exome

AF:

0.111

Gnomad ASJ exome

AF:

0.291

Gnomad EAS exome

AF:

0.0702

Gnomad SAS exome

AF:

0.166

Gnomad FIN exome

AF:

0.191

Gnomad NFE exome

AF:

0.212

Gnomad OTH exome

AF:

0.216

GnomAD4 exome

AF:

0.208

AC:

303346

AN:

1461372

Hom.:

35281

Cov.:

AF XY:

0.206

AC XY:

149958

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.587

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.300

Gnomad4 EAS exome

AF:

0.0502

Gnomad4 SAS exome

AF:

0.169

Gnomad4 FIN exome

AF:

0.191

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.226

GnomAD4 genome

AF:

0.299

AC:

45477

AN:

152106

Hom.:

9076

Cov.:

AF XY:

0.291

AC XY:

21635

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.568

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.303

Gnomad4 EAS

AF:

0.0688

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.211

Gnomad4 OTH

AF:

0.267

Alfa

AF:

0.227

Hom.:

7852

Bravo

AF:

0.308

Asia WGS

AF:

0.155

AC:

539

AN:

3478

EpiCase

AF:

0.217

EpiControl

AF:

0.216

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.3

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.0020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over