19-54128255-C-T

Variant names:

• chr19-54128255-C-T
• rs34990810
• NM_015629.4:c.1074-50C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0588 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF31	NM_015629.4	MANE Select	c.1074-50C>T		intron	N/A	NP_056444.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF31	ENST00000321030.9	TSL:1 MANE Select	c.1074-50C>T		intron	N/A	ENSP00000324122.4
	PRPF31	ENST00000466404.5	TSL:2	n.998C>T		non_coding_transcript_exon	Exon 9 of 11
	PRPF31	ENST00000391755.1	TSL:5	c.1056-50C>T		intron	N/A	ENSP00000375635.1

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

GnomAD2 exomes AF: 0.0486 AC: 7755 AN: 159466 AF XY: 0.0497

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 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

African (AFR) AF: 0.0113 AC: 369 AN: 32710

American (AMR) AF: 0.0250 AC: 893 AN: 35790

Ashkenazi Jewish (ASJ) AF: 0.0714 AC: 1796 AN: 25150

East Asian (EAS) AF: 0.0105 AC: 394 AN: 37698

South Asian (SAS) AF: 0.0534 AC: 4273 AN: 79956

European-Finnish (FIN) AF: 0.0713 AC: 3435 AN: 48178

Middle Eastern (MID) AF: 0.0293 AC: 124 AN: 4234

European-Non Finnish (NFE) AF: 0.0606 AC: 65699 AN: 1083320

Other (OTH) AF: 0.0525 AC: 3054 AN: 58214

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

African (AFR) AF: 0.0121 AC: 504 AN: 41522

American (AMR) AF: 0.0344 AC: 526 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0749 AC: 260 AN: 3472

East Asian (EAS) AF: 0.00912 AC: 47 AN: 5156

South Asian (SAS) AF: 0.0534 AC: 258 AN: 4828

European-Finnish (FIN) AF: 0.0743 AC: 787 AN: 10586

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0603 AC: 4097 AN: 67938

Other (OTH) AF: 0.0303 AC: 64 AN: 2112

Alfa AF: 0.0523 Hom.: 51

Bravo AF: 0.0380

Asia WGS AF: 0.0310 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.56
DANN	Benign	0.89
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34990810; hg19: chr19-54631630; COSMIC: COSV107351044; COSMIC: COSV107351044;