rs4859564

chr4-75882914-A-Gchr4-75882914-A-T

Variant summary

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

The NM_006239.3(PPEF2):c.933+12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 1,595,880 control chromosomes in the GnomAD database, including 759,006 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 0.86 (59439 hom., cov: 31)
  • Exomes 𝑓: 0.98 (699567 hom.)
• Consequence: PPEF2 NM_006239.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740

Genes affected

PPEF2 (HGNC:9244): (protein phosphatase with EF-hand domain 2) This gene encodes a member of the serine/threonine protein phosphatase with EF-hand motif family. The protein contains a protein phosphatase catalytic domain, and at least two EF-hand calcium-binding motifs in its C terminus. Although its substrate(s) is unknown, the encoded protein, which is expressed specifically in photoreceptors and the pineal, has been suggested to play a role in the visual system. This gene shares high sequence similarity with the Drosophila retinal degeneration C (rdgC) gene. [provided by RefSeq, Jul 2008]

LOC105377285 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPEF2	NM_006239.3	c.933+12T>C		intron_variant		ENST00000286719.12
LOC105377285	XR_938895.3	n.399+4139A>G		intron_variant, non_coding_transcript_variant
PPEF2	XM_011532039.3	c.933+12T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPEF2	ENST00000286719.12	c.933+12T>C		intron_variant		1	NM_006239.3	P1
PPEF2	ENST00000511880.7	c.*516+12T>C		intron_variant, NMD_transcript_variant		1
PPEF2	ENST00000513324.1	n.429T>C		non_coding_transcript_exon_variant	3/3	3
PPEF2	ENST00000515552.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130945 AN: 152046 Hom.: 59433 Cov.: 31

Gnomad AFR AF: 0.538

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.990

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.889

GnomAD3 exomes AF: 0.957 AC: 228982 AN: 239254 Hom.: 111216 AF XY: 0.967 AC XY: 124927 AN XY: 129226

Gnomad AFR exome AF: 0.528

Gnomad AMR exome AF: 0.964

Gnomad ASJ exome AF: 0.955

Gnomad EAS exome AF: 0.995

Gnomad SAS exome AF: 0.991

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.994

Gnomad OTH exome AF: 0.971

GnomAD4 exome AF: 0.982 AC: 1417188 AN: 1443716 Hom.: 699567 Cov.: 41 AF XY: 0.983 AC XY: 704387 AN XY: 716528

Gnomad4 AFR exome AF: 0.513

Gnomad4 AMR exome AF: 0.960

Gnomad4 ASJ exome AF: 0.956

Gnomad4 EAS exome AF: 0.997

Gnomad4 SAS exome AF: 0.990

Gnomad4 FIN exome AF: 0.999

Gnomad4 NFE exome AF: 0.996

Gnomad4 OTH exome AF: 0.957

GnomAD4 genome AF: 0.861 AC: 130997 AN: 152164 Hom.: 59439 Cov.: 31 AF XY: 0.866 AC XY: 64397 AN XY: 74404

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.928

Gnomad4 ASJ AF: 0.949

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.990

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.994

Gnomad4 OTH AF: 0.887

Alfa AF: 0.915 Hom.: 9219

Bravo AF: 0.842

Asia WGS AF: 0.947 AC: 3293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.7
Dann	Benign	0.67

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: rs4859564; hg19: chr4-76804067;