Variant 9-113275672-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001244926.2(PRPF4):c.-72C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,550,452 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 1 hom. )

Consequence

PRPF4
NM_001244926.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.30

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]

PRPF4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 9-113275672-C-T is Benign according to our data. Variant chr9-113275672-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3042380.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 166 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF4	NM_001244926.2 link	c.-72C>T		5_prime_UTR_premature_start_codon_gain_variant	1/14	ENST00000374198.5	NP_001231855.1	O43172-2Q5T1M7
PRPF4	NM_001244926.2 link	c.-72C>T		5_prime_UTR_variant	1/14	ENST00000374198.5	NP_001231855.1	O43172-2Q5T1M7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRPF4	ENST00000374198 link	c.-72C>T	5_prime_UTR_premature_start_codon_gain_variant	1/14	1	NM_001244926.2	ENSP00000363313.4	O43172-2
PRPF4	ENST00000374199 link	c.-72C>T	5_prime_UTR_premature_start_codon_gain_variant	1/14	1		ENSP00000363315.4	O43172-1
PRPF4	ENST00000374198 link	c.-72C>T	5_prime_UTR_variant	1/14	1	NM_001244926.2	ENSP00000363313.4	O43172-2
PRPF4	ENST00000374199 link	c.-72C>T	5_prime_UTR_variant	1/14	1		ENSP00000363315.4	O43172-1

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

166

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00179

Gnomad OTH

AF:

0.00239

GnomAD4 exome

AF:

0.00166

AC:

2322

AN:

1398128

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

1068

AN XY:

692342

show subpopulations

Gnomad4 AFR exome

AF:

0.000319

Gnomad4 AMR exome

AF:

0.00160

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000373

Gnomad4 FIN exome

AF:

0.0000403

Gnomad4 NFE exome

AF:

0.00198

Gnomad4 OTH exome

AF:

0.00203

GnomAD4 genome

AF:

0.00109

AC:

166

AN:

152324

Hom.:

Cov.:

AF XY:

0.000993

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00179

Gnomad4 OTH

AF:

0.00236

Bravo

AF:

0.00121

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRPF4-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 02, 2019

This 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.87

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

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