rs4278208

Positions:

• chr9-101167497-A-G

Variant summary

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

The NM_207299.2(PLPPR1):​c.-45-17953A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 151,474 control chromosomes in the GnomAD database, including 2,077 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 0.15 (2077 hom., cov: 28)
• Consequence: PLPPR1 NM_207299.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220

Genes affected

PLPPR1 (HGNC:25993): (phospholipid phosphatase related 1) This gene encodes a member of the plasticity-related gene (PRG) family. Members of the PRG family mediate lipid phosphate phosphatase activity in neurons and are known to be involved in neuronal plasticity. The protein encoded by this gene does not perform its function through enzymatic phospholipid degradation. This gene is strongly expressed in brain. It shows dynamic expression regulation during brain development and neuronal excitation. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLPPR1	NM_207299.2	c.-45-17953A>G		intron_variant		ENST00000374874.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLPPR1	ENST00000374874.8	c.-45-17953A>G		intron_variant		1	NM_207299.2	P1
PLPPR1	ENST00000456287.5	c.-45-17953A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22644 AN: 151354 Hom.: 2072 Cov.: 28

Gnomad AFR AF: 0.0535

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0757

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.150 AC: 22654 AN: 151474 Hom.: 2077 Cov.: 28 AF XY: 0.147 AC XY: 10839 AN XY: 73976

Gnomad4 AFR AF: 0.0533

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.0761

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.170

Alfa AF: 0.185 Hom.: 676

Bravo AF: 0.148

Asia WGS AF: 0.0950 AC: 329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.62

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: rs4278208; hg19: chr9-103929779;