rs10853869

Variant names:

• chr19-54127722-G-A
• rs10853869
• NM_015629.4:c.946-351G>A

Variant summary

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

The NM_015629.4(PRPF31):​c.946-351G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,936 control chromosomes in the GnomAD database, including 7,646 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 0.31 (7646 hom., cov: 33)
• Consequence: PRPF31 NM_015629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• 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 Gene-Disease associations (from GenCC):

• PRPF31-related retinopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 11

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.946-351G>A		intron_variant	Intron 9 of 13	ENST00000321030.9	NP_056444.3
PRPF31	XM_006723137.5	c.946-351G>A		intron_variant	Intron 9 of 13		XP_006723200.1
PRPF31	XM_047438587.1	c.974-351G>A		intron_variant	Intron 9 of 9		XP_047294543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9	c.946-351G>A		intron_variant	Intron 9 of 13	1	NM_015629.4	ENSP00000324122.4

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47130 AN: 151820 Hom.: 7625 Cov.: 33

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.0632

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.311 AC: 47190 AN: 151936 Hom.: 7646 Cov.: 33 AF XY: 0.308 AC XY: 22863 AN XY: 74258

African (AFR) AF: 0.387 AC: 16030 AN: 41456

American (AMR) AF: 0.328 AC: 5003 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1096 AN: 3472

East Asian (EAS) AF: 0.0632 AC: 324 AN: 5130

South Asian (SAS) AF: 0.289 AC: 1386 AN: 4794

European-Finnish (FIN) AF: 0.285 AC: 3012 AN: 10570

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19396 AN: 67936

Other (OTH) AF: 0.321 AC: 679 AN: 2114

Alfa AF: 0.290 Hom.: 11410

Bravo AF: 0.314

Asia WGS AF: 0.229 AC: 799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.56
DANN	Benign	0.75
PhyloP100		-1.2
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: rs10853869; hg19: chr19-54631097;