rs475827

Positions:

• chrX-103775144-G-A

Variant summary

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

The ENST00000494475.5(PLP1):​c.-144+689G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 111,566 control chromosomes in the GnomAD database, including 1,700 homozygotes. There are 6,244 hemizygotes in GnomAD. 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 0.20 (1700 hom., 6244 hem., cov: 23)
• Consequence: PLP1 ENST00000494475.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

Genes affected

PLP1 (HGNC:9086): (proteolipid protein 1) This gene encodes a transmembrane proteolipid protein that is the predominant component of myelin. The encoded protein may play a role in the compaction, stabilization, and maintenance of myelin sheaths, as well as in oligodendrocyte development and axonal survival. Mutations in this gene cause Pelizaeus-Merzbacher disease and spastic paraplegia type 2. Alternatively splicing results in multiple transcript variants, including the DM20 splice variant. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLP1	ENST00000434483.5	c.-144+782G>A		intron_variant		2
PLP1	ENST00000494475.5	c.-144+689G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.197 AC: 21964 AN: 111511 Hom.: 1700 Cov.: 23 AF XY: 0.185 AC XY: 6234 AN XY: 33707

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.0408

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.157

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.197 AC: 21980 AN: 111566 Hom.: 1700 Cov.: 23 AF XY: 0.185 AC XY: 6244 AN XY: 33772

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.0409

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.180

Alfa AF: 0.226 Hom.: 17848

Bravo AF: 0.197

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs475827; hg19: chrX-103030072;