rs1409322

Variant names:

• chr10-13600086-G-A
• rs1409322
• NM_003675.4:c.145-158G>A

Variant summary

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

The NM_003675.4(PRPF18):​c.145-158G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,184 control chromosomes in the GnomAD database, including 47,130 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 0.78 (47130 hom., cov: 33)
• Consequence: PRPF18 NM_003675.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49
• Publications: 3 publications found

Genes affected

PRPF18 (HGNC:17351): (pre-mRNA processing factor 18) Pre-mRNA splicing occurs in 2 sequential transesterification steps. The protein encoded by this gene is found to be essential for the catalytic step II in pre-mRNA splicing process. It is found in the spliceosome, and contains seven WD repeats, which function in protein-protein interactions. This protein has a sequence similarity to the yeast splicing factor Prp18. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF18	NM_003675.4	c.145-158G>A		intron_variant	Intron 2 of 9	ENST00000378572.8	NP_003666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF18	ENST00000378572.8	c.145-158G>A		intron_variant	Intron 2 of 9	1	NM_003675.4	ENSP00000367835.3
PRPF18	ENST00000417658.5	c.127-158G>A		intron_variant	Intron 4 of 9	5		ENSP00000392142.1
PRPF18	ENST00000320054.4	c.100-158G>A		intron_variant	Intron 3 of 6	5		ENSP00000367824.1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119131 AN: 152066 Hom.: 47099 Cov.: 33

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.783 AC: 119205 AN: 152184 Hom.: 47130 Cov.: 33 AF XY: 0.785 AC XY: 58439 AN XY: 74416

African (AFR) AF: 0.669 AC: 27751 AN: 41474

American (AMR) AF: 0.821 AC: 12552 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2584 AN: 3472

East Asian (EAS) AF: 0.867 AC: 4489 AN: 5180

South Asian (SAS) AF: 0.755 AC: 3647 AN: 4830

European-Finnish (FIN) AF: 0.839 AC: 8889 AN: 10592

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56609 AN: 68020

Other (OTH) AF: 0.775 AC: 1639 AN: 2116

Alfa AF: 0.813 Hom.: 64002

Bravo AF: 0.779

Asia WGS AF: 0.755 AC: 2631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.021
DANN	Benign	0.61
PhyloP100		-2.5
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: rs1409322; hg19: chr10-13642086;