17-15230388-CAG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000304.4(PMP22):c.*527_*528del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 160,766 control chromosomes in the GnomAD database, including 10,480 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (9823 hom., cov: 0)
  • Exomes 𝑓: 0.36 (657 hom.)
• Consequence: PMP22 NM_000304.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.618

Genes affected

PMP22 (HGNC:9118): (peripheral myelin protein 22) This gene encodes an integral membrane protein that is a major component of myelin in the peripheral nervous system. Studies suggest two alternately used promoters drive tissue-specific expression. Various mutations of this gene are causes of Charcot-Marie-Tooth disease Type IA, Dejerine-Sottas syndrome, and hereditary neuropathy with liability to pressure palsies. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-15230388-CAG-C is Benign according to our data. Variant chr17-15230388-CAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 321853.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMP22	NM_000304.4	c.*527_*528del		3_prime_UTR_variant	5/5	ENST00000312280.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMP22	ENST00000312280.9	c.*527_*528del		3_prime_UTR_variant	5/5	1	NM_000304.4	P1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53096 AN: 151874 Hom.: 9821 Cov.: 0

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.357 AC: 3136 AN: 8774 Hom.: 657 AF XY: 0.360 AC XY: 1673 AN XY: 4648

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.434

Gnomad4 EAS exome AF: 0.228

Gnomad4 SAS exome AF: 0.346

Gnomad4 FIN exome AF: 0.343

Gnomad4 NFE exome AF: 0.371

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.349 AC: 53108 AN: 151992 Hom.: 9823 Cov.: 0 AF XY: 0.350 AC XY: 26040 AN XY: 74308

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.357

Alfa AF: 0.374 Hom.: 1325

Bravo AF: 0.345

Asia WGS AF: 0.319 AC: 1109 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary liability to pressure palsies Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Charcot-Marie-Tooth disease, type I Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs71699667; hg19: chr17-15133705;