chr19-54121847-C-T

Variant names:

• chr19-54121847-C-T
• rs113691122
• NM_015629.4:c.239-13C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015629.4(PRPF31):​c.239-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00412 in 1,604,744 control chromosomes in the GnomAD database, including 248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (126 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (122 hom.)
• Consequence: PRPF31 NM_015629.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.476
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 19-54121847-C-T is Benign according to our data. Variant chr19-54121847-C-T is described in ClinVar as Benign. ClinVar VariationId is 330096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0747 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.239-13C>T		intron	N/A	NP_056444.3
	PRPF31-AS1	NR_186329.1		n.564G>A		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF31	ENST00000321030.9	TSL:1 MANE Select	c.239-13C>T		intron	N/A	ENSP00000324122.4	Q8WWY3-1
	PRPF31	ENST00000951323.1		c.239-13C>T		intron	N/A	ENSP00000621382.1
	PRPF31	ENST00000861422.1		c.332-13C>T		intron	N/A	ENSP00000531481.1

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3395 AN: 152224 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.0771

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00975

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0177

GnomAD2 exomes AF: 0.00572 AC: 1338 AN: 233922 AF XY: 0.00427

Gnomad AFR exome AF: 0.0808

Gnomad AMR exome AF: 0.00388

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000171

Gnomad FIN exome AF: 0.0000515

Gnomad NFE exome AF: 0.000152

Gnomad OTH exome AF: 0.00208

GnomAD4 exome AF: 0.00221 AC: 3209 AN: 1452402 Hom.: 122 Cov.: 32 AF XY: 0.00191 AC XY: 1376 AN XY: 721674

African (AFR) AF: 0.0793 AC: 2642 AN: 33310

American (AMR) AF: 0.00452 AC: 196 AN: 43362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25912

East Asian (EAS) AF: 0.0000763 AC: 3 AN: 39300

South Asian (SAS) AF: 0.0000946 AC: 8 AN: 84604

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52488

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5762

European-Non Finnish (NFE) AF: 0.0000659 AC: 73 AN: 1107628

Other (OTH) AF: 0.00455 AC: 273 AN: 60036

GnomAD4 genome AF: 0.0223 AC: 3397 AN: 152342 Hom.: 126 Cov.: 32 AF XY: 0.0219 AC XY: 1634 AN XY: 74498

African (AFR) AF: 0.0769 AC: 3198 AN: 41570

American (AMR) AF: 0.00967 AC: 148 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68036

Other (OTH) AF: 0.0175 AC: 37 AN: 2110

Alfa AF: 0.0136 Hom.: 13

Bravo AF: 0.0260

Asia WGS AF: 0.00462 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.5
DANN	Benign	0.73
PhyloP100		0.48
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: rs113691122; hg19: chr19-54625226; COSMIC: COSV58087473; COSMIC: COSV58087473;