10-13625731-G-T

Position:

• chr10-13625731-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000378572.8(PRPF18):​c.949-4529G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,078 control chromosomes in the GnomAD database, including 24,598 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 0.56 (24598 hom., cov: 33)
• Consequence: PRPF18 ENST00000378572.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF18	NM_003675.4	c.949-4529G>T		intron_variant		ENST00000378572.8	NP_003666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF18	ENST00000378572.8	c.949-4529G>T		intron_variant		1	NM_003675.4	ENSP00000367835	P1
PRPF18	ENST00000601460.5	c.577+9178G>T		intron_variant		5		ENSP00000473200
PRPF18	ENST00000595538.5	c.24-4529G>T		intron_variant, NMD_transcript_variant		5		ENSP00000469146

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85687 AN: 151960 Hom.: 24585 Cov.: 33

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.564 AC: 85733 AN: 152078 Hom.: 24598 Cov.: 33 AF XY: 0.558 AC XY: 41511 AN XY: 74336

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.585

Alfa AF: 0.613 Hom.: 34981

Bravo AF: 0.572

Asia WGS AF: 0.454 AC: 1582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.79
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs7089227; hg19: chr10-13667731;