19-54124246-C-T

Variant names:

• chr19-54124246-C-T
• rs11670086
• NM_015629.4:c.698-253C>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.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
• Publications: 7 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-AS1 (HGNC:40700): (PRPF31 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

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.698-253C>T		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.698-253C>T		intron	N/A	ENSP00000324122.4	Q8WWY3-1
	PRPF31	ENST00000951323.1		c.698-253C>T		intron	N/A	ENSP00000621382.1
	PRPF31	ENST00000861422.1		c.791-253C>T		intron	N/A	ENSP00000531481.1

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

African (AFR) AF: 0.132 AC: 1730 AN: 13062

American (AMR) AF: 0.217 AC: 4141 AN: 19122

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 2091 AN: 13890

East Asian (EAS) AF: 0.0303 AC: 949 AN: 31362

South Asian (SAS) AF: 0.152 AC: 7086 AN: 46572

European-Finnish (FIN) AF: 0.113 AC: 3368 AN: 29744

Middle Eastern (MID) AF: 0.172 AC: 352 AN: 2042

European-Non Finnish (NFE) AF: 0.129 AC: 38392 AN: 298174

Other (OTH) AF: 0.145 AC: 3913 AN: 27054

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

African (AFR) AF: 0.130 AC: 5407 AN: 41532

American (AMR) AF: 0.193 AC: 2949 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3468

East Asian (EAS) AF: 0.0447 AC: 231 AN: 5166

South Asian (SAS) AF: 0.136 AC: 658 AN: 4826

European-Finnish (FIN) AF: 0.111 AC: 1174 AN: 10600

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8731 AN: 68000

Other (OTH) AF: 0.154 AC: 324 AN: 2108

Alfa AF: 0.116 Hom.: 636

Bravo AF: 0.139

Asia WGS AF: 0.130 AC: 454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.4
DANN	Benign	0.46
PhyloP100		0.51
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: rs11670086; hg19: chr19-54627625;