6-4052318-G-A

Position:

• chr6-4052318-G-A

Variant summary

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

The NM_003913.5(PRPF4B):​c.2312+224G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 151,920 control chromosomes in the GnomAD database, including 32,800 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 0.65 (32800 hom., cov: 31)
• Consequence: PRPF4B NM_003913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.972

Genes affected

PRPF4B (HGNC:17346): (pre-mRNA processing factor kinase PRP4K) Pre-mRNA splicing occurs in two sequential transesterification steps, and the protein encoded by this gene is thought to be involved in pre-mRNA splicing and in signal transduction. This protein belongs to a kinase family that includes serine/arginine-rich protein-specific kinases and cyclin-dependent kinases (CDKs). This protein is regarded as a CDK-like kinase (Clk) with homology to mitogen-activated protein kinases (MAPKs). [provided by RefSeq, Jul 2008]

FAM217A (HGNC:21362): (family with sequence similarity 217 member A)

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 (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF4B	NM_003913.5	c.2312+224G>A		intron_variant		ENST00000337659.11	NP_003904.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF4B	ENST00000337659.11	c.2312+224G>A		intron_variant		1	NM_003913.5	ENSP00000337194	P1

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99320 AN: 151802 Hom.: 32776 Cov.: 31

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.654 AC: 99392 AN: 151920 Hom.: 32800 Cov.: 31 AF XY: 0.655 AC XY: 48671 AN XY: 74252

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.712

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.663

Alfa AF: 0.661 Hom.: 3980

Bravo AF: 0.651

Asia WGS AF: 0.739 AC: 2572 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	4.5
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3747763; hg19: chr6-4052552;