rs1058572

Variant names:

• chr19-54123785-G-A
• rs1058572
• NM_015629.4:c.564G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_015629.4(PRPF31):​c.564G>A​(p.Glu188Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0266 in 1,611,796 control chromosomes in the GnomAD database, including 695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (58 hom., cov: 33)
  • Exomes 𝑓: 0.027 (637 hom.)
• Consequence: PRPF31 NM_015629.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.15
• Publications: 8 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 19-54123785-G-A is Benign according to our data. Variant chr19-54123785-G-A is described in ClinVar as Benign. ClinVar VariationId is 330098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0221 (3369/152304) while in subpopulation NFE AF = 0.0323 (2198/68022). AF 95% confidence interval is 0.0312. There are 58 homozygotes in GnomAd4. There are 1644 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3369 AD gene.

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.564G>A	p.Glu188Glu	synonymous	Exon 7 of 14	NP_056444.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF31	ENST00000321030.9	TSL:1 MANE Select	c.564G>A	p.Glu188Glu	synonymous	Exon 7 of 14	ENSP00000324122.4
	PRPF31	ENST00000951323.1		c.564G>A	p.Glu188Glu	synonymous	Exon 7 of 15	ENSP00000621382.1
	PRPF31	ENST00000861422.1		c.657G>A	p.Glu219Glu	synonymous	Exon 8 of 15	ENSP00000531481.1

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3367 AN: 152186 Hom.: 58 Cov.: 33

Gnomad AFR AF: 0.00521

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.0530

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0323

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.0226 AC: 5608 AN: 248026 AF XY: 0.0222

Gnomad AFR exome AF: 0.00484

Gnomad AMR exome AF: 0.0106

Gnomad ASJ exome AF: 0.0199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0557

Gnomad NFE exome AF: 0.0320

Gnomad OTH exome AF: 0.0227

GnomAD4 exome AF: 0.0271 AC: 39575 AN: 1459492 Hom.: 637 Cov.: 35 AF XY: 0.0263 AC XY: 19092 AN XY: 726196

African (AFR) AF: 0.00442 AC: 148 AN: 33478

American (AMR) AF: 0.0107 AC: 476 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 513 AN: 26132

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39694

South Asian (SAS) AF: 0.00422 AC: 364 AN: 86244

European-Finnish (FIN) AF: 0.0515 AC: 2645 AN: 51348

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5762

European-Non Finnish (NFE) AF: 0.0307 AC: 34110 AN: 1111814

Other (OTH) AF: 0.0215 AC: 1299 AN: 60336

GnomAD4 genome AF: 0.0221 AC: 3369 AN: 152304 Hom.: 58 Cov.: 33 AF XY: 0.0221 AC XY: 1644 AN XY: 74464

African (AFR) AF: 0.00520 AC: 216 AN: 41570

American (AMR) AF: 0.0144 AC: 221 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 72 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4830

European-Finnish (FIN) AF: 0.0530 AC: 562 AN: 10604

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0323 AC: 2198 AN: 68022

Other (OTH) AF: 0.0156 AC: 33 AN: 2114

Alfa AF: 0.0277 Hom.: 193

Bravo AF: 0.0183

Asia WGS AF: 0.00318 AC: 13 AN: 3478

EpiCase AF: 0.0293

EpiControl AF: 0.0280

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.94
PhyloP100		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs1058572; hg19: chr19-54627164;