19-54126322-T-C

Variant names:

• chr19-54126322-T-C
• rs254272
• NM_015629.4:c.856-206T>C

Variant summary

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

The NM_015629.4(PRPF31):​c.856-206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,098 control chromosomes in the GnomAD database, including 2,556 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 0.18 (2556 hom., cov: 33)
• Consequence: PRPF31 NM_015629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.803
• Publications: 8 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, Labcorp Genetics (formerly Invitae), G2P
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF31	NM_015629.4	MANE Select	c.856-206T>C		intron	N/A	NP_056444.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF31	ENST00000321030.9	TSL:1 MANE Select	c.856-206T>C		intron	N/A	ENSP00000324122.4	Q8WWY3-1
	PRPF31	ENST00000951323.1		c.856-206T>C		intron	N/A	ENSP00000621382.1
	PRPF31	ENST00000861422.1		c.949-206T>C		intron	N/A	ENSP00000531481.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26637 AN: 151978 Hom.: 2552 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.175 AC: 26655 AN: 152098 Hom.: 2556 Cov.: 33 AF XY: 0.175 AC XY: 13038 AN XY: 74332

African (AFR) AF: 0.123 AC: 5126 AN: 41512

American (AMR) AF: 0.135 AC: 2059 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3468

East Asian (EAS) AF: 0.245 AC: 1267 AN: 5162

South Asian (SAS) AF: 0.194 AC: 934 AN: 4812

European-Finnish (FIN) AF: 0.262 AC: 2773 AN: 10574

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13504 AN: 67964

Other (OTH) AF: 0.156 AC: 330 AN: 2110

Alfa AF: 0.182 Hom.: 5128

Bravo AF: 0.161

Asia WGS AF: 0.257 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.34
PhyloP100		-0.80
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: rs254272; hg19: chr19-54629697; COSMIC: COSV58086876; COSMIC: COSV58086876;