rs10733604

Variant names:

• chr9-113279983-A-C
• rs10733604
• NM_001244926.2:c.392+852A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-113279983-A-C
• chr9-113279983-A-G
• chr9-113279983-A-T

Variant summary

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

The NM_001244926.2(PRPF4):​c.392+852A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,094 control chromosomes in the GnomAD database, including 58,689 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 0.88 (58689 hom., cov: 30)
• Consequence: PRPF4 NM_001244926.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416
• Publications: 4 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]

PRPF4 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 70

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• inherited retinal dystrophy

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244926.2. 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.392+852A>C		intron	N/A	NP_001231855.1	O43172-2
	PRPF4	NM_004697.5		c.395+852A>C		intron	N/A	NP_004688.2
	PRPF4	NM_001322266.2		c.-374+852A>C		intron	N/A	NP_001309195.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF4	ENST00000374198.5	TSL:1 MANE Select	c.392+852A>C		intron	N/A	ENSP00000363313.4	O43172-2
	PRPF4	ENST00000374199.9	TSL:1	c.395+852A>C		intron	N/A	ENSP00000363315.4	O43172-1
	PRPF4	ENST00000921177.1		c.392+852A>C		intron	N/A	ENSP00000591236.1

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133350 AN: 151976 Hom.: 58637 Cov.: 30

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.890

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

GnomAD4 genome AF: 0.878 AC: 133463 AN: 152094 Hom.: 58689 Cov.: 30 AF XY: 0.875 AC XY: 65040 AN XY: 74334

African (AFR) AF: 0.908 AC: 37657 AN: 41484

American (AMR) AF: 0.845 AC: 12898 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 3131 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5173 AN: 5182

South Asian (SAS) AF: 0.919 AC: 4428 AN: 4818

European-Finnish (FIN) AF: 0.784 AC: 8283 AN: 10568

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.866 AC: 58883 AN: 67986

Other (OTH) AF: 0.892 AC: 1883 AN: 2112

Alfa AF: 0.874 Hom.: 109326

Bravo AF: 0.883

Asia WGS AF: 0.953 AC: 3316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.7
DANN	Benign	0.64
PhyloP100		-0.42
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: rs10733604; hg19: chr9-116042263;