Variant X-103785471-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000533.5(PLP1):c.5-111T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 645,540 control chromosomes in the GnomAD database, including 47,332 homozygotes. There are 88,687 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.49 ( 9912 hom., 15600 hem., cov: 23)

Exomes 𝑓: 0.44 ( 37420 hom. 73087 hem. )

Consequence

PLP1
NM_000533.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0150

Variant links:

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]

PLP1 links:

PLP1 (HGNC:):

PLP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant X-103785471-T-C is Benign according to our data. Variant chrX-103785471-T-C is described in ClinVar as [Benign]. Clinvar id is 670482.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLP1	NM_000533.5 linkuse as main transcript	c.5-111T>C		intron_variant		ENST00000621218.5	NP_000524.3	P60201-1A8K9L3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLP1	ENST00000621218.5 linkuse as main transcript	c.5-111T>C		intron_variant		1	NM_000533.5	ENSP00000484450.1		P60201-1

Frequencies

GnomAD3 genomes

AF:

0.489

AC:

54105

AN:

110737

Hom.:

9908

Cov.:

AF XY:

0.471

AC XY:

15559

AN XY:

33001

show subpopulations

Gnomad AFR

AF:

0.621

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.482

Gnomad ASJ

AF:

0.531

Gnomad EAS

AF:

0.378

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.445

Gnomad OTH

AF:

0.494

GnomAD4 exome

AF:

0.442

AC:

236257

AN:

534747

Hom.:

37420

AF XY:

0.432

AC XY:

73087

AN XY:

169019

show subpopulations

Gnomad4 AFR exome

AF:

0.638

Gnomad4 AMR exome

AF:

0.518

Gnomad4 ASJ exome

AF:

0.503

Gnomad4 EAS exome

AF:

0.362

Gnomad4 SAS exome

AF:

0.264

Gnomad4 FIN exome

AF:

0.416

Gnomad4 NFE exome

AF:

0.452

Gnomad4 OTH exome

AF:

0.461

GnomAD4 genome

AF:

0.489

AC:

54146

AN:

110793

Hom.:

9912

Cov.:

AF XY:

0.472

AC XY:

15600

AN XY:

33067

show subpopulations

Gnomad4 AFR

AF:

0.621

Gnomad4 AMR

AF:

0.481

Gnomad4 ASJ

AF:

0.531

Gnomad4 EAS

AF:

0.378

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.394

Gnomad4 NFE

AF:

0.445

Gnomad4 OTH

AF:

0.496

Alfa

AF:

0.449

Hom.:

10501

Bravo

AF:

0.507

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.3

DANN

Benign

0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over