chr19-54126833-A-C

Variant names:

• chr19-54126833-A-C
• rs10424816
• NM_015629.4:c.945+216A>C

Variant summary

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

The NM_015629.4(PRPF31):​c.945+216A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,142 control chromosomes in the GnomAD database, including 12,372 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 0.40 (12372 hom., cov: 33)
• Consequence: PRPF31 NM_015629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.559
• Publications: 13 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.945+216A>C		intron_variant	Intron 9 of 13	ENST00000321030.9	NP_056444.3
PRPF31	XM_006723137.5	c.945+216A>C		intron_variant	Intron 9 of 13		XP_006723200.1
PRPF31	XM_047438587.1	c.973+216A>C		intron_variant	Intron 9 of 9		XP_047294543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9	c.945+216A>C		intron_variant	Intron 9 of 13	1	NM_015629.4	ENSP00000324122.4

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60374 AN: 152024 Hom.: 12352 Cov.: 33

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.397 AC: 60445 AN: 152142 Hom.: 12372 Cov.: 33 AF XY: 0.400 AC XY: 29735 AN XY: 74384

African (AFR) AF: 0.442 AC: 18332 AN: 41486

American (AMR) AF: 0.429 AC: 6548 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1269 AN: 3472

East Asian (EAS) AF: 0.588 AC: 3037 AN: 5164

South Asian (SAS) AF: 0.415 AC: 2005 AN: 4828

European-Finnish (FIN) AF: 0.440 AC: 4670 AN: 10606

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23392 AN: 67992

Other (OTH) AF: 0.377 AC: 797 AN: 2112

Alfa AF: 0.352 Hom.: 16023

Bravo AF: 0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.2
PhyloP100		0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10424816; hg19: chr19-54630208;