19-54127773-C-T

Variant names:

• chr19-54127773-C-T
• rs8102427
• NM_015629.4:c.946-300C>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.946-300C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,142 control chromosomes in the GnomAD database, including 6,160 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 0.26 (6160 hom., cov: 33)
• Consequence: PRPF31 NM_015629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.946-300C>T		intron_variant	Intron 9 of 13	ENST00000321030.9	NP_056444.3
PRPF31	XM_006723137.5	c.946-300C>T		intron_variant	Intron 9 of 13		XP_006723200.1
PRPF31	XM_047438587.1	c.974-300C>T		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.946-300C>T		intron_variant	Intron 9 of 13	1	NM_015629.4	ENSP00000324122.4

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40176 AN: 152024 Hom.: 6160 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.264 AC: 40168 AN: 152142 Hom.: 6160 Cov.: 33 AF XY: 0.259 AC XY: 19296 AN XY: 74378

African (AFR) AF: 0.117 AC: 4842 AN: 41512

American (AMR) AF: 0.261 AC: 3987 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1209 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1094 AN: 5164

South Asian (SAS) AF: 0.268 AC: 1293 AN: 4818

European-Finnish (FIN) AF: 0.239 AC: 2534 AN: 10600

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24165 AN: 67970

Other (OTH) AF: 0.289 AC: 612 AN: 2116

Alfa AF: 0.324 Hom.: 4104

Bravo AF: 0.261

Asia WGS AF: 0.193 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.85
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8102427; hg19: chr19-54631148;