NM_015629.4:c.946-691C>G

Variant names:

• chr19-54127382-C-G
• rs254271
• NM_015629.4:c.946-691C>G

Variant summary

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

The NM_015629.4(PRPF31):​c.946-691C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 151,984 control chromosomes in the GnomAD database, including 35,358 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 0.68 (35358 hom., cov: 31)
• Consequence: PRPF31 NM_015629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92
• Publications: 16 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 = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.946-691C>G		intron_variant	Intron 9 of 13	ENST00000321030.9	NP_056444.3
PRPF31	XM_006723137.5	c.946-691C>G		intron_variant	Intron 9 of 13		XP_006723200.1
PRPF31	XM_047438587.1	c.974-691C>G		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.946-691C>G		intron_variant	Intron 9 of 13	1	NM_015629.4	ENSP00000324122.4

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103071 AN: 151866 Hom.: 35314 Cov.: 31

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.679 AC: 103169 AN: 151984 Hom.: 35358 Cov.: 31 AF XY: 0.674 AC XY: 50094 AN XY: 74272

African (AFR) AF: 0.767 AC: 31806 AN: 41448

American (AMR) AF: 0.680 AC: 10375 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2308 AN: 3470

East Asian (EAS) AF: 0.570 AC: 2938 AN: 5158

South Asian (SAS) AF: 0.620 AC: 2987 AN: 4820

European-Finnish (FIN) AF: 0.608 AC: 6424 AN: 10564

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44125 AN: 67950

Other (OTH) AF: 0.679 AC: 1432 AN: 2110

Alfa AF: 0.523 Hom.: 1288

Bravo AF: 0.687

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.099
PhyloP100		-2.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs254271; hg19: chr19-54630757;