Variant 17-15229797-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.60

Variant links:

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]

PMP22 links:

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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=-0.31).

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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 41 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMP22	NM_000304.4 link	c.*1120T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000312280.9	NP_000295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMP22	ENST00000312280 link	c.*1120T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_000304.4	ENSP00000308937.3		Q01453

Frequencies

GnomAD3 genomes

AF:

0.0174

AC:

2643

AN:

152220

Hom.:

Cov.:

show subpopulations

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:

AN:

400

Hom.:

Cov.:

AF XY:

0.0289

AC XY:

AN XY:

242

show subpopulations

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.:

Cov.:

AF XY:

0.0167

AC XY:

1244

AN XY:

74486

show subpopulations

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.:

Bravo

AF:

0.0152

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hereditary liability to pressure palsies

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Charcot-Marie-Tooth disease, type I

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

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

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