19-54122676-G-C

Position:

• chr19-54122676-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.420+82G>C		intron_variant		ENST00000321030.9	NP_056444.3
PRPF31-AS1	XR_007067340.1	n.1002C>G		non_coding_transcript_exon_variant	2/3
PRPF31	XM_006723137.5	c.420+82G>C		intron_variant			XP_006723200.1
PRPF31	XM_047438587.1	c.420+82G>C		intron_variant			XP_047294543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9	c.420+82G>C		intron_variant		1	NM_015629.4	ENSP00000324122	P1
PRPF31-AS1	ENST00000452097.1	n.2668C>G		non_coding_transcript_exon_variant	1/4	2

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

Gnomad4 AFR exome AF: 0.876

Gnomad4 AMR exome AF: 0.771

Gnomad4 ASJ exome AF: 0.765

Gnomad4 EAS exome AF: 0.781

Gnomad4 SAS exome AF: 0.804

Gnomad4 FIN exome AF: 0.781

Gnomad4 NFE exome AF: 0.808

Gnomad4 OTH exome AF: 0.811

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

Gnomad4 AFR AF: 0.874

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.782

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.795

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.818

Alfa AF: 0.811 Hom.: 6237

Bravo AF: 0.819

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.37
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

Publications

LitVar

Other links and lift over

dbSNP: rs56220912; hg19: chr19-54626055;