rs2556367

Positions:

• chr19-54128716-G-A
• chr19-54128716-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.1146+339G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 152,092 control chromosomes in the GnomAD database, including 196 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 0.045 (196 hom., cov: 31)
• Consequence: PRPF31 NM_015629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.06 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.1146+339G>A		intron_variant		ENST00000321030.9	NP_056444.3
PRPF31	XM_006723137.5	c.1146+339G>A		intron_variant			XP_006723200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9	c.1146+339G>A		intron_variant		1	NM_015629.4	ENSP00000324122.4
PRPF31	ENST00000391755.1	c.1128+339G>A		intron_variant		5		ENSP00000375635.1
PRPF31	ENST00000419967.5	c.1146+339G>A		intron_variant		5		ENSP00000405166.2
PRPF31	ENST00000466404.5	n.1120+339G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6800 AN: 151974 Hom.: 196 Cov.: 31

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.00970

Gnomad SAS AF: 0.0445

Gnomad FIN AF: 0.0773

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0615

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0447 AC: 6804 AN: 152092 Hom.: 196 Cov.: 31 AF XY: 0.0449 AC XY: 3336 AN XY: 74350

Gnomad4 AFR AF: 0.0145

Gnomad4 AMR AF: 0.0354

Gnomad4 ASJ AF: 0.0749

Gnomad4 EAS AF: 0.00991

Gnomad4 SAS AF: 0.0444

Gnomad4 FIN AF: 0.0773

Gnomad4 NFE AF: 0.0616

Gnomad4 OTH AF: 0.0327

Alfa AF: 0.0183 Hom.: 14

Bravo AF: 0.0394

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.36
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2556367; hg19: chr19-54632091;