rs231018

Variant names:

• chr17-15262264-A-C
• rs231018
• NM_000304.4:c.-34-1503T>G

Your query was ambiguous. Multiple possible variants found:

• chr17-15262264-A-C
• chr17-15262264-A-G
• chr17-15262264-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease type 1A

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine, Ambry Genetics
• hereditary neuropathy with liability to pressure palsies

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• Charcot-Marie-Tooth disease type 1E

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)
• Charcot-Marie-Tooth disease type 3

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000265445 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000304.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMP22	NM_000304.4	MANE Select	c.-34-1503T>G		intron	N/A	NP_000295.1
	PMP22	NM_001281455.2		c.-35+161T>G		intron	N/A	NP_001268384.1
	PMP22	NM_001281456.2		c.-30-1507T>G		intron	N/A	NP_001268385.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMP22	ENST00000312280.9	TSL:1 MANE Select	c.-34-1503T>G		intron	N/A	ENSP00000308937.3
	PMP22	ENST00000395938.7	TSL:1	c.-35+165T>G		intron	N/A	ENSP00000379269.3
	PMP22	ENST00000494511.7	TSL:1	c.-27+2890T>G		intron	N/A	ENSP00000462782.2

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

African (AFR) AF: 0.813 AC: 33785 AN: 41536

American (AMR) AF: 0.574 AC: 8769 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1940 AN: 3470

East Asian (EAS) AF: 0.654 AC: 3360 AN: 5136

South Asian (SAS) AF: 0.509 AC: 2458 AN: 4828

European-Finnish (FIN) AF: 0.425 AC: 4498 AN: 10590

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.526 AC: 35789 AN: 67976

Other (OTH) AF: 0.605 AC: 1276 AN: 2108

Alfa AF: 0.563 Hom.: 42690

Bravo AF: 0.631

Asia WGS AF: 0.591 AC: 2052 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.34
DANN	Benign	0.50
PhyloP100		-3.2
PromoterAI		0.016	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs231018; hg19: chr17-15165581;