rs12985735

Variant names:

• chr19-54120169-G-A
• rs12985735
• NM_015629.4:c.238+1536G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-54120169-G-A
• chr19-54120169-G-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.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 NM_015629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 8 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 (NFE) allele frequency at 95% confidence interval = 0.487 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.238+1536G>A		intron	N/A	NP_056444.3
	PRPF31-AS1	NR_186329.1		n.799C>T		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF31	ENST00000321030.9	TSL:1 MANE Select	c.238+1536G>A		intron	N/A	ENSP00000324122.4
	PRPF31-AS1	ENST00000452097.1	TSL:2	n.3500C>T		non_coding_transcript_exon	Exon 4 of 4
	PRPF31	ENST00000391755.1	TSL:5	c.238+1536G>A		intron	N/A	ENSP00000375635.1

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.500 AC: 2 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.400 AC: 4 AN: 10

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.508 AC: 66 AN: 130

Other (OTH) AF: 0.333 AC: 2 AN: 6

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

African (AFR) AF: 0.126 AC: 5247 AN: 41516

American (AMR) AF: 0.346 AC: 5278 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1505 AN: 3472

East Asian (EAS) AF: 0.447 AC: 2307 AN: 5158

South Asian (SAS) AF: 0.416 AC: 2001 AN: 4808

European-Finnish (FIN) AF: 0.423 AC: 4473 AN: 10578

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33403 AN: 67966

Other (OTH) AF: 0.389 AC: 819 AN: 2108

Alfa AF: 0.445 Hom.: 22296

Bravo AF: 0.348

Asia WGS AF: 0.411 AC: 1427 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	0.24
DANN	Benign	0.46
PhyloP100		-1.3
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: rs12985735; hg19: chr19-54623549;