rs35705606

Positions:

• chr19-54116140-A-G
• chr19-54116140-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRPF31	NM_015629.4	c.-9+343A>G		intron_variant		ENST00000321030.9
PRPF31	XM_006723137.5	c.-39+343A>G		intron_variant
PRPF31	XM_047438587.1	c.-9+343A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF31	ENST00000321030.9	c.-9+343A>G		intron_variant		1	NM_015629.4	P1

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

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0534

Gnomad4 ASJ AF: 0.0784

Gnomad4 EAS AF: 0.0107

Gnomad4 SAS AF: 0.0448

Gnomad4 FIN AF: 0.0811

Gnomad4 NFE AF: 0.0626

Gnomad4 OTH AF: 0.0635

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.2
DANN	Benign	0.49

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: rs35705606; hg19: chr19-54619520;