14-45112961-C-T

Position:

• chr14-45112961-C-T

Variant summary

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

The NM_017922.4(PRPF39):​c.1757+459C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0605 in 152,146 control chromosomes in the GnomAD database, including 960 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 0.060 (960 hom., cov: 32)
• Consequence: PRPF39 NM_017922.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

Genes affected

PRPF39 (HGNC:20314): (pre-mRNA processing factor 39) Predicted to be involved in mRNA 5'-splice site recognition. Predicted to be part of U1 snRNP; U2-type prespliceosome; and commitment complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRPF39	NM_017922.4	c.1757+459C>T		intron_variant		ENST00000355765.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF39	ENST00000355765.11	c.1757+459C>T		intron_variant		1	NM_017922.4	P1

Frequencies

GnomAD3 genomes AF: 0.0602 AC: 9154 AN: 152028 Hom.: 950 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0221

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0605 AC: 9199 AN: 152146 Hom.: 960 Cov.: 32 AF XY: 0.0583 AC XY: 4336 AN XY: 74374

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.0220

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00107

Gnomad4 OTH AF: 0.0469

Alfa AF: 0.0139 Hom.: 147

Bravo AF: 0.0683

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.0
DANN	Benign	0.65

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: rs17115814; hg19: chr14-45582164;