rs56220912

Variant names:

• chr19-54122676-G-C
• rs56220912
• NM_015629.4:c.420+82G>C

Variant summary

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

The NM_015629.4(PRPF31):​c.420+82G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 1,110,294 control chromosomes in the GnomAD database, including 360,973 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 0.82 (51147 hom., cov: 31)
  • Exomes 𝑓: 0.80 (309826 hom.)
• Consequence: PRPF31 NM_015629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861
• Publications: 10 publications found

Genes affected

PRPF31 (HGNC:15446): (pre-mRNA processing factor 31) This gene encodes a component of the spliceosome complex and is one of several retinitis pigmentosa-causing genes. When the gene product is added to the spliceosome complex, activation occurs.[provided by RefSeq, Jan 2009]

PRPF31-AS1 (HGNC:40700): (PRPF31 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015629.4. 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
	PRPF31	NM_015629.4	MANE Select	c.420+82G>C		intron	N/A	NP_056444.3
	PRPF31-AS1	NR_186329.1		n.-34C>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF31	ENST00000321030.9	TSL:1 MANE Select	c.420+82G>C		intron	N/A	ENSP00000324122.4	Q8WWY3-1
	PRPF31	ENST00000951323.1		c.420+82G>C		intron	N/A	ENSP00000621382.1
	PRPF31	ENST00000861422.1		c.513+82G>C		intron	N/A	ENSP00000531481.1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124462 AN: 151950 Hom.: 51092 Cov.: 31

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.817

GnomAD4 exome AF: 0.804 AC: 770006 AN: 958226 Hom.: 309826 Cov.: 13 AF XY: 0.803 AC XY: 400161 AN XY: 498028

African (AFR) AF: 0.876 AC: 20620 AN: 23530

American (AMR) AF: 0.771 AC: 33755 AN: 43806

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 17660 AN: 23078

East Asian (EAS) AF: 0.781 AC: 29223 AN: 37412

South Asian (SAS) AF: 0.804 AC: 61330 AN: 76290

European-Finnish (FIN) AF: 0.781 AC: 39678 AN: 50832

Middle Eastern (MID) AF: 0.732 AC: 3431 AN: 4690

European-Non Finnish (NFE) AF: 0.808 AC: 528761 AN: 654732

Other (OTH) AF: 0.811 AC: 35548 AN: 43856

GnomAD4 genome AF: 0.819 AC: 124575 AN: 152068 Hom.: 51147 Cov.: 31 AF XY: 0.815 AC XY: 60574 AN XY: 74328

African (AFR) AF: 0.874 AC: 36268 AN: 41498

American (AMR) AF: 0.799 AC: 12197 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2715 AN: 3472

East Asian (EAS) AF: 0.810 AC: 4171 AN: 5148

South Asian (SAS) AF: 0.795 AC: 3832 AN: 4818

European-Finnish (FIN) AF: 0.779 AC: 8232 AN: 10568

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54546 AN: 67984

Other (OTH) AF: 0.818 AC: 1730 AN: 2114

Alfa AF: 0.811 Hom.: 6237

Bravo AF: 0.819

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.37
PhyloP100		-0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Other links and lift over

dbSNP: rs56220912; hg19: chr19-54626055;