17-15230689-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_000304.4(PMP22):c.*228G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0606 in 560,482 control chromosomes in the GnomAD database, including 1,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (343 hom., cov: 33)
  • Exomes 𝑓: 0.062 (963 hom.)
• Consequence: PMP22 NM_000304.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 7.05

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 17-15230689-C-T is Benign according to our data. Variant chr17-15230689-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 321855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.08 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMP22	NM_000304.4	c.*228G>A		3_prime_UTR_variant	5/5	ENST00000312280.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMP22	ENST00000312280.9	c.*228G>A		3_prime_UTR_variant	5/5	1	NM_000304.4	P1

Frequencies

GnomAD3 genomes AF: 0.0556 AC: 8464 AN: 152150 Hom.: 343 Cov.: 33

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0573

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0986

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.0612

GnomAD3 exomes AF: 0.0504 AC: 3238 AN: 64210 Hom.: 127 AF XY: 0.0496 AC XY: 1582 AN XY: 31916

Gnomad AFR exome AF: 0.0141

Gnomad AMR exome AF: 0.0494

Gnomad ASJ exome AF: 0.0466

Gnomad EAS exome AF: 0.000249

Gnomad SAS exome AF: 0.0130

Gnomad FIN exome AF: 0.103

Gnomad NFE exome AF: 0.0777

Gnomad OTH exome AF: 0.0670

GnomAD4 exome AF: 0.0625 AC: 25506 AN: 408214 Hom.: 963 Cov.: 3 AF XY: 0.0600 AC XY: 12930 AN XY: 215510

Gnomad4 AFR exome AF: 0.0133

Gnomad4 AMR exome AF: 0.0479

Gnomad4 ASJ exome AF: 0.0458

Gnomad4 EAS exome AF: 0.0000732

Gnomad4 SAS exome AF: 0.0172

Gnomad4 FIN exome AF: 0.0987

Gnomad4 NFE exome AF: 0.0781

Gnomad4 OTH exome AF: 0.0620

GnomAD4 genome AF: 0.0556 AC: 8466 AN: 152268 Hom.: 343 Cov.: 33 AF XY: 0.0559 AC XY: 4163 AN XY: 74454

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.0573

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0153

Gnomad4 FIN AF: 0.0986

Gnomad4 NFE AF: 0.0818

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0707 Hom.: 87

Bravo AF: 0.0515

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

- -

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	18
Dann	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1804193; hg19: chr17-15134006;