17-15262264-A-C

Position:

• chr17-15262264-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000304.4(PMP22):​c.-34-1503T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,130 control chromosomes in the GnomAD database, including 29,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.61 (29536 hom., cov: 33)
• Consequence: PMP22 NM_000304.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.20

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-15262264-A-C is Benign according to our data. Variant chr17-15262264-A-C is described in ClinVar as [Benign]. Clinvar id is 1230134.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMP22	NM_000304.4	c.-34-1503T>G		intron_variant		ENST00000312280.9	NP_000295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMP22	ENST00000312280.9	c.-34-1503T>G		intron_variant		1	NM_000304.4	ENSP00000308937.3

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92577 AN: 152012 Hom.: 29475 Cov.: 33

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.603

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.609 AC: 92690 AN: 152130 Hom.: 29536 Cov.: 33 AF XY: 0.604 AC XY: 44919 AN XY: 74380

Gnomad4 AFR AF: 0.813

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.605

Alfa AF: 0.539 Hom.: 7505

Bravo AF: 0.631

Asia WGS AF: 0.591 AC: 2052 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 11, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.34
DANN	Benign	0.50

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: rs231018; hg19: chr17-15165581;