chr19-54124246-C-T

Position:

• chr19-54124246-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015629.4(PRPF31):​c.698-253C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 633,210 control chromosomes in the GnomAD database, including 5,814 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 0.13 (1392 hom., cov: 32)
  • Exomes 𝑓: 0.13 (4422 hom.)
• Consequence: PRPF31 NM_015629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509

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-AS1 (HGNC:40700): (PRPF31 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRPF31	NM_015629.4	c.698-253C>T		intron_variant		ENST00000321030.9
PRPF31-AS1	XR_007067340.1	n.88-656G>A		intron_variant, non_coding_transcript_variant
PRPF31	XM_006723137.5	c.698-253C>T		intron_variant
PRPF31	XM_047438587.1	c.698-253C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF31	ENST00000321030.9	c.698-253C>T		intron_variant		1	NM_015629.4	P1
PRPF31-AS1	ENST00000452097.1	n.1098G>A		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20193 AN: 152070 Hom.: 1382 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0444

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.129 AC: 62022 AN: 481022 Hom.: 4422 Cov.: 5 AF XY: 0.130 AC XY: 32823 AN XY: 252606

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.217

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.0303

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.133 AC: 20228 AN: 152188 Hom.: 1392 Cov.: 32 AF XY: 0.132 AC XY: 9800 AN XY: 74374

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.0447

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.154

Alfa AF: 0.115 Hom.: 562

Bravo AF: 0.139

Asia WGS AF: 0.130 AC: 454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.4
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs11670086; hg19: chr19-54627625;