9-113275652-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000374199(PRPF4):​c.-92A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,447,598 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000090 ( 1 hom. )

Consequence

PRPF4
ENST00000374199 5_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.78
Variant links:
Genes affected
PRPF4 (HGNC:17349): (pre-mRNA splicing tri-snRNP complex factor PRPF4) The protein encoded by this gene is part of a heteromeric complex that binds U4, U5, and U6 small nuclear RNAs and is involved in pre-mRNA splicing. The encoded protein also is a mitotic checkpoint protein and a regulator of chemoresistance in human ovarian cancer. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 9-113275652-A-G is Benign according to our data. Variant chr9-113275652-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 999774.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 40 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PRPF4NM_001244926.2 linkc.-92A>G upstream_gene_variant ENST00000374198.5 NP_001231855.1 O43172-2Q5T1M7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PRPF4ENST00000374199 linkc.-92A>G 5_prime_UTR_variant 1/141 ENSP00000363315.4 O43172-1
PRPF4ENST00000374198.5 linkc.-92A>G upstream_gene_variant 1 NM_001244926.2 ENSP00000363313.4 O43172-2

Frequencies

GnomAD3 genomes
AF:
0.000263
AC:
40
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000869
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000896
AC:
116
AN:
1295320
Hom.:
1
Cov.:
18
AF XY:
0.0000810
AC XY:
52
AN XY:
642172
show subpopulations
Gnomad4 AFR exome
AF:
0.00180
Gnomad4 AMR exome
AF:
0.0000837
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000187
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000222
Gnomad4 OTH exome
AF:
0.000352
GnomAD4 genome
AF:
0.000263
AC:
40
AN:
152278
Hom.:
0
Cov.:
32
AF XY:
0.000255
AC XY:
19
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.000866
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000285
Hom.:
0
Bravo
AF:
0.000336

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

PRPF4-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJul 29, 2020This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 14, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.67
DANN
Benign
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs375348528; hg19: chr9-116037932; API