4-75882304-G-A

Position:

• chr4-75882304-G-A

Variant summary

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

The NM_006239.3(PPEF2):​c.933+622C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 152,156 control chromosomes in the GnomAD database, including 59,916 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 0.87 (59916 hom., cov: 32)
• Consequence: PPEF2 NM_006239.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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=-0.98).
• 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	Protein	UniProt
PPEF2	NM_006239.3	c.933+622C>T		intron_variant		ENST00000286719.12	NP_006230.2
LOC105377285	XR_938895.3	n.399+3529G>A		intron_variant, non_coding_transcript_variant
PPEF2	XM_011532039.3	c.933+622C>T		intron_variant			XP_011530341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPEF2	ENST00000286719.12	c.933+622C>T		intron_variant		1	NM_006239.3	ENSP00000286719	P1
PPEF2	ENST00000511880.7	c.*517-319C>T		intron_variant, NMD_transcript_variant		1		ENSP00000426186

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131790 AN: 152038 Hom.: 59914 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.995

Gnomad OTH AF: 0.894

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

GnomAD4 genome AF: 0.866 AC: 131835 AN: 152156 Hom.: 59916 Cov.: 32 AF XY: 0.871 AC XY: 64795 AN XY: 74414

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.932

Gnomad4 ASJ AF: 0.949

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.990

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.995

Gnomad4 OTH AF: 0.891

Alfa AF: 0.977 Hom.: 108563

Bravo AF: 0.848

Asia WGS AF: 0.946 AC: 3291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.41
DANN	Benign	0.51

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: rs7694386; hg19: chr4-76803457;