chr19-54116140-A-G

Variant names:

• chr19-54116140-A-G
• rs35705606
• NM_015629.4:c.-9+343A>G

Variant summary

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

The NM_015629.4(PRPF31):​c.-9+343A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0833 in 148,880 control chromosomes in the GnomAD database, including 611 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 0.083 (611 hom., cov: 30)
• Consequence: PRPF31 NM_015629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326
• Publications: 3 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 (AFR) allele frequency at 95% confidence interval = 0.142 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.-9+343A>G		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.-9+343A>G		intron	N/A	ENSP00000324122.4
	PRPF31	ENST00000419967.5	TSL:5	c.-9+343A>G		intron	N/A	ENSP00000405166.2
	PRPF31	ENST00000445811.5	TSL:5	c.-32+343A>G		intron	N/A	ENSP00000395894.1

Frequencies

GnomAD3 genomes AF: 0.0833 AC: 12398 AN: 148762 Hom.: 612 Cov.: 30

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0588

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.0105

Gnomad SAS AF: 0.0450

Gnomad FIN AF: 0.0811

Gnomad MID AF: 0.0563

Gnomad NFE AF: 0.0626

Gnomad OTH AF: 0.0642

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

GnomAD4 genome AF: 0.0833 AC: 12409 AN: 148880 Hom.: 611 Cov.: 30 AF XY: 0.0830 AC XY: 6019 AN XY: 72518

African (AFR) AF: 0.145 AC: 5844 AN: 40204

American (AMR) AF: 0.0534 AC: 792 AN: 14826

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 271 AN: 3456

East Asian (EAS) AF: 0.0107 AC: 53 AN: 4964

South Asian (SAS) AF: 0.0448 AC: 211 AN: 4706

European-Finnish (FIN) AF: 0.0811 AC: 810 AN: 9988

Middle Eastern (MID) AF: 0.0606 AC: 16 AN: 264

European-Non Finnish (NFE) AF: 0.0626 AC: 4228 AN: 67508

Other (OTH) AF: 0.0635 AC: 131 AN: 2062

Alfa AF: 0.0685 Hom.: 54

Bravo AF: 0.0831

Asia WGS AF: 0.0340 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.2
DANN	Benign	0.49
PhyloP100		0.33
PromoterAI		-0.049	Neutral
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: rs35705606; hg19: chr19-54619520;