10-13625731-G-T

Variant names:

• chr10-13625731-G-T
• rs7089227
• NM_003675.4:c.949-4529G>T

Variant summary

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

The NM_001395875.1(PRPF18):​c.976-4529G>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 NM_001395875.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395875.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF18	NM_003675.4	MANE Select	c.949-4529G>T		intron	N/A	NP_003666.1
	PRPF18	NM_001395875.1		c.976-4529G>T		intron	N/A	NP_001382804.1
	PRPF18	NM_001395876.1		c.931-4529G>T		intron	N/A	NP_001382805.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF18	ENST00000378572.8	TSL:1 MANE Select	c.949-4529G>T		intron	N/A	ENSP00000367835.3
	PRPF18	ENST00000937338.1		c.1023+3959G>T		intron	N/A	ENSP00000607397.1
	PRPF18	ENST00000855616.1		c.976-4529G>T		intron	N/A	ENSP00000525675.1

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

African (AFR) AF: 0.459 AC: 19049 AN: 41464

American (AMR) AF: 0.612 AC: 9357 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2033 AN: 3472

East Asian (EAS) AF: 0.550 AC: 2842 AN: 5164

South Asian (SAS) AF: 0.419 AC: 2022 AN: 4824

European-Finnish (FIN) AF: 0.535 AC: 5655 AN: 10564

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.627 AC: 42632 AN: 67988

Other (OTH) AF: 0.585 AC: 1236 AN: 2114

Alfa AF: 0.609 Hom.: 47791

Bravo AF: 0.572

Asia WGS AF: 0.454 AC: 1582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.79
DANN	Benign	0.75
PhyloP100		-0.13
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: rs7089227; hg19: chr10-13667731;