17-15229797-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_000304.4(PMP22):c.*1120T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0174 in 152,738 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (41 hom., cov: 33)
  • Exomes 𝑓: 0.030 (1 hom.)
• Consequence: PMP22 NM_000304.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 5.60

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 17-15229797-A-G is Benign according to our data. Variant chr17-15229797-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 321845.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-15229797-A-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0173 (2641/152338) while in subpopulation NFE AF= 0.0264 (1794/68028). AF 95% confidence interval is 0.0254. There are 41 homozygotes in gnomad4. There are 1244 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 41 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMP22	NM_000304.4	c.*1120T>C		3_prime_UTR_variant	5/5	ENST00000312280.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMP22	ENST00000312280.9	c.*1120T>C		3_prime_UTR_variant	5/5	1	NM_000304.4	P1

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2643 AN: 152220 Hom.: 41 Cov.: 33

Gnomad AFR AF: 0.00444

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0264

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.0300 AC: 12 AN: 400 Hom.: 1 Cov.: 0 AF XY: 0.0289 AC XY: 7 AN XY: 242

Gnomad4 FIN exome AF: 0.0258

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0173 AC: 2641 AN: 152338 Hom.: 41 Cov.: 33 AF XY: 0.0167 AC XY: 1244 AN XY: 74486

Gnomad4 AFR AF: 0.00442

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0209

Gnomad4 FIN AF: 0.0271

Gnomad4 NFE AF: 0.0264

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.0218 Hom.: 19

Bravo AF: 0.0152

Asia WGS AF: 0.00635 AC: 23 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	17
Dann	Benign	0.92

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: rs11654383; hg19: chr17-15133114;