rs12985735

Positions:

• chr19-54120169-G-A
• chr19-54120169-G-T

Variant summary

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

The ENST00000321030.9(PRPF31):​c.238+1536G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,240 control chromosomes in the GnomAD database, including 12,059 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 0.37 (12039 hom., cov: 32)
  • Exomes 𝑓: 0.46 (20 hom.)
• Consequence: PRPF31 ENST00000321030.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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 (NFE) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.238+1536G>A		intron_variant		ENST00000321030.9	NP_056444.3
PRPF31-AS1	XR_007067340.1	n.1842+1667C>T		intron_variant, non_coding_transcript_variant
PRPF31	XM_006723137.5	c.238+1536G>A		intron_variant			XP_006723200.1
PRPF31	XM_047438587.1	c.238+1536G>A		intron_variant			XP_047294543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9	c.238+1536G>A		intron_variant		1	NM_015629.4	ENSP00000324122	P1
PRPF31-AS1	ENST00000452097.1	n.3500C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55563 AN: 151958 Hom.: 12040 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.463 AC: 76 AN: 164 Hom.: 20 Cov.: 0 AF XY: 0.466 AC XY: 54 AN XY: 116

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.508

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.365 AC: 55558 AN: 152076 Hom.: 12039 Cov.: 32 AF XY: 0.363 AC XY: 26984 AN XY: 74340

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.389

Alfa AF: 0.460 Hom.: 17382

Bravo AF: 0.348

Asia WGS AF: 0.411 AC: 1427 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	0.24
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: rs12985735; hg19: chr19-54623549;