rs4768412

chr12-42475338-C-T

Variant summary

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

The NM_153026.3(PRICKLE1):c.-48-2774G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,112 control chromosomes in the GnomAD database, including 8,314 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 0.32 (8314 hom., cov: 33)
• Consequence: PRICKLE1 NM_153026.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.54

Genes affected

PRICKLE1 (HGNC:17019): (prickle planar cell polarity protein 1) This gene encodes a nuclear receptor that may be a negative regulator of the Wnt/beta-catenin signaling pathway. The encoded protein localizes to the nuclear membrane and has been implicated in the nuclear trafficking of the transcription repressors REST/NRSF and REST4. Mutations in this gene have been linked to progressive myoclonus epilepsy. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 3. [provided by RefSeq, Sep 2009]

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 (NFE) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRICKLE1	NM_153026.3	c.-48-2774G>A		intron_variant		ENST00000345127.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRICKLE1	ENST00000345127.9	c.-48-2774G>A		intron_variant		1	NM_153026.3	P1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48557 AN: 151994 Hom.: 8312 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.319 AC: 48579 AN: 152112 Hom.: 8314 Cov.: 33 AF XY: 0.318 AC XY: 23667 AN XY: 74356

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.315

Alfa AF: 0.358 Hom.: 4761

Bravo AF: 0.315

Asia WGS AF: 0.221 AC: 771 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	0.16
Dann	Benign	0.63

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: rs4768412; hg19: chr12-42869140;