chr17-15230689-C-T
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
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
NM_000304.4 3_prime_UTR
Scores
2
Clinical Significance
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]
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ACMG classification
Classification made for transcript
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: 8464AN: 152150Hom.: 343 Cov.: 33
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GnomAD3 exomes AF: 0.0504 AC: 3238AN: 64210Hom.: 127 AF XY: 0.0496 AC XY: 1582AN XY: 31916
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GnomAD4 exome AF: 0.0625 AC: 25506AN: 408214Hom.: 963 Cov.: 3 AF XY: 0.0600 AC XY: 12930AN XY: 215510
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GnomAD4 genome ? AF: 0.0556 AC: 8466AN: 152268Hom.: 343 Cov.: 33 AF XY: 0.0559 AC XY: 4163AN XY: 74454
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
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
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at