rs34990810

Positions:

• chr19-54128255-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015629.4(PRPF31):​c.1074-50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 1,557,362 control chromosomes in the GnomAD database, including 2,649 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 0.043 (185 hom., cov: 32)
  • Exomes 𝑓: 0.057 (2464 hom.)
• Consequence: PRPF31 NM_015629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.0588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.1074-50C>T		intron_variant		ENST00000321030.9	NP_056444.3
PRPF31	XM_006723137.5	c.1074-50C>T		intron_variant			XP_006723200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9	c.1074-50C>T		intron_variant		1	NM_015629.4	ENSP00000324122.4
PRPF31	ENST00000391755.1	c.1056-50C>T		intron_variant		5		ENSP00000375635.1
PRPF31	ENST00000419967.5	c.1074-50C>T		intron_variant		5		ENSP00000405166.2
PRPF31	ENST00000466404.5	n.998C>T		non_coding_transcript_exon_variant	9/11	2

Frequencies

GnomAD3 genomes AF: 0.0434 AC: 6601 AN: 151996 Hom.: 185 Cov.: 32

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0344

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.00890

Gnomad SAS AF: 0.0536

Gnomad FIN AF: 0.0743

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0603

Gnomad OTH AF: 0.0306

GnomAD3 exomes AF: 0.0486 AC: 7755 AN: 159466 Hom.: 213 AF XY: 0.0497 AC XY: 4236 AN XY: 85154

Gnomad AFR exome AF: 0.0104

Gnomad AMR exome AF: 0.0250

Gnomad ASJ exome AF: 0.0718

Gnomad EAS exome AF: 0.00604

Gnomad SAS exome AF: 0.0525

Gnomad FIN exome AF: 0.0752

Gnomad NFE exome AF: 0.0613

Gnomad OTH exome AF: 0.0475

GnomAD4 exome AF: 0.0570 AC: 80037 AN: 1405250 Hom.: 2464 Cov.: 64 AF XY: 0.0567 AC XY: 39328 AN XY: 693410

Gnomad4 AFR exome AF: 0.0113

Gnomad4 AMR exome AF: 0.0250

Gnomad4 ASJ exome AF: 0.0714

Gnomad4 EAS exome AF: 0.0105

Gnomad4 SAS exome AF: 0.0534

Gnomad4 FIN exome AF: 0.0713

Gnomad4 NFE exome AF: 0.0606

Gnomad4 OTH exome AF: 0.0525

GnomAD4 genome AF: 0.0434 AC: 6606 AN: 152112 Hom.: 185 Cov.: 32 AF XY: 0.0437 AC XY: 3251 AN XY: 74356

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.0344

Gnomad4 ASJ AF: 0.0749

Gnomad4 EAS AF: 0.00912

Gnomad4 SAS AF: 0.0534

Gnomad4 FIN AF: 0.0743

Gnomad4 NFE AF: 0.0603

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0532 Hom.: 51

Bravo AF: 0.0380

Asia WGS AF: 0.0310 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.56
DANN	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs34990810; hg19: chr19-54631630;