rs541873609

Variant names:

• chr9-113275629-TTGTCAGTGACGCACTTCC-T
• rs541873609
• ENST00000374199.9:c.-114_-97delTGTCAGTGACGCACTTCC

Your query was ambiguous. Multiple possible variants found:

• chr9-113275629-TTGTCAGTGACGCACTTCC-T
• chr9-113275629-TTGTCAGTGACGCACTTCC-TTGTCAGTGACGCACTTCCTGTCAGTGACGCACTTCC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000374199.9(PRPF4):​c.-114_-97delTGTCAGTGACGCACTTCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,280,224 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: PRPF4 ENST00000374199.9 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts P:1 U:2
• Conservation: PhyloP100: 0.365
• Publications: 2 publications found

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]

CDC26 (HGNC:17839): (cell division cycle 26) The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Cdc26, a component of cell cycle anaphase-promoting complex (APC). APC is composed of a group of highly conserved proteins and functions as a cell cycle-regulated ubiquitin-protein ligase. APC thus is responsible for the cell cycle regulated proteolysis of various proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 16 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000374199.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF4	NM_001244926.2	MANE Select	c.-114_-97delTGTCAGTGACGCACTTCC		upstream_gene	N/A	NP_001231855.1	O43172-2
	CDC26	NM_139286.4	MANE Select	c.-417_-400delGGAAGTGCGTCACTGACA		upstream_gene	N/A	NP_644815.1	Q8NHZ8
	PRPF4	NM_004697.5		c.-114_-97delTGTCAGTGACGCACTTCC		upstream_gene	N/A	NP_004688.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF4	ENST00000374199.9	TSL:1	c.-114_-97delTGTCAGTGACGCACTTCC		5_prime_UTR	Exon 1 of 14	ENSP00000363315.4	O43172-1
	PRPF4	ENST00000374199.9	TSL:1	c.-114_-97delTGTCAGTGACGCACTTCC		non_coding_transcript	N/A	ENSP00000363315.4	O43172-1
	PRPF4	ENST00000374198.5	TSL:1 MANE Select	c.-114_-97delTGTCAGTGACGCACTTCC		upstream_gene	N/A	ENSP00000363313.4	O43172-2

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000337 AC: 38 AN: 1127914 Hom.: 0 AF XY: 0.0000266 AC XY: 15 AN XY: 563130

African (AFR) AF: 0.0000797 AC: 2 AN: 25094

American (AMR) AF: 0.0000633 AC: 2 AN: 31592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18708

East Asian (EAS) AF: 0.000175 AC: 6 AN: 34246

South Asian (SAS) AF: 0.0000148 AC: 1 AN: 67464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4588

European-Non Finnish (NFE) AF: 0.0000269 AC: 23 AN: 856226

Other (OTH) AF: 0.0000831 AC: 4 AN: 48144

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74472

African (AFR) AF: 0.000120 AC: 5 AN: 41572

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)
1	-	-	Retinitis pigmentosa 70 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36
Mutation Taster		=106/194	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs541873609; hg19: chr9-116037909;