19-54124083-A-G

Variant names:

• chr19-54124083-A-G
• rs56234781
• NM_015629.4:c.697+165A>G

Variant summary

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

The NM_015629.4(PRPF31):​c.697+165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,396,988 control chromosomes in the GnomAD database, including 460,945 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 0.82 (51822 hom., cov: 32)
  • Exomes 𝑓: 0.81 (409123 hom.)
• Consequence: PRPF31 NM_015629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.24
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.697+165A>G		intron_variant	Intron 7 of 13	ENST00000321030.9	NP_056444.3
PRPF31	XM_006723137.5	c.697+165A>G		intron_variant	Intron 7 of 13		XP_006723200.1
PRPF31	XM_047438587.1	c.697+165A>G		intron_variant	Intron 7 of 9		XP_047294543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9	c.697+165A>G		intron_variant	Intron 7 of 13	1	NM_015629.4	ENSP00000324122.4

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125259 AN: 152000 Hom.: 51766 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.822

GnomAD4 exome AF: 0.810 AC: 1008608 AN: 1244870 Hom.: 409123 Cov.: 20 AF XY: 0.810 AC XY: 492904 AN XY: 608154

African (AFR) AF: 0.892 AC: 25027 AN: 28072

American (AMR) AF: 0.776 AC: 20072 AN: 25876

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 15078 AN: 19636

East Asian (EAS) AF: 0.781 AC: 27160 AN: 34788

South Asian (SAS) AF: 0.805 AC: 52151 AN: 64770

European-Finnish (FIN) AF: 0.782 AC: 24206 AN: 30966

Middle Eastern (MID) AF: 0.748 AC: 3325 AN: 4444

European-Non Finnish (NFE) AF: 0.812 AC: 798711 AN: 983894

Other (OTH) AF: 0.818 AC: 42878 AN: 52424

GnomAD4 genome AF: 0.824 AC: 125373 AN: 152118 Hom.: 51822 Cov.: 32 AF XY: 0.820 AC XY: 60942 AN XY: 74352

African (AFR) AF: 0.886 AC: 36789 AN: 41500

American (AMR) AF: 0.804 AC: 12276 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2716 AN: 3468

East Asian (EAS) AF: 0.809 AC: 4169 AN: 5156

South Asian (SAS) AF: 0.795 AC: 3838 AN: 4826

European-Finnish (FIN) AF: 0.779 AC: 8256 AN: 10594

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.805 AC: 54702 AN: 67978

Other (OTH) AF: 0.823 AC: 1740 AN: 2114

Alfa AF: 0.757 Hom.: 2228

Bravo AF: 0.825

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.42
PhyloP100		-3.2

Splicing

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

Other links and lift over

dbSNP: rs56234781; hg19: chr19-54627462;