chr10-13624931-T-G

Position:

• chr10-13624931-T-G

Variant summary

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

The NM_003675.4(PRPF18):​c.949-5329T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,130 control chromosomes in the GnomAD database, including 2,938 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 0.19 (2938 hom., cov: 33)
• Consequence: PRPF18 NM_003675.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF18	NM_003675.4	c.949-5329T>G		intron_variant		ENST00000378572.8	NP_003666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF18	ENST00000378572.8	c.949-5329T>G		intron_variant		1	NM_003675.4	ENSP00000367835	P1
PRPF18	ENST00000601460.5	c.577+8378T>G		intron_variant		5		ENSP00000473200
PRPF18	ENST00000595538.5	c.24-5329T>G		intron_variant, NMD_transcript_variant		5		ENSP00000469146

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29151 AN: 152012 Hom.: 2932 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.192 AC: 29175 AN: 152130 Hom.: 2938 Cov.: 33 AF XY: 0.200 AC XY: 14907 AN XY: 74386

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.166

Alfa AF: 0.186 Hom.: 5519

Bravo AF: 0.175

Asia WGS AF: 0.250 AC: 872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.77

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: rs7098174; hg19: chr10-13666931;