rs8065610

Variant names:

• chr17-15272253-C-A
• rs8065610
• ENST00000674868.1:c.-592G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-15272253-C-A
• chr17-15272253-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000674868.1(PMP22):​c.-592G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,110 control chromosomes in the GnomAD database, including 8,372 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8372 hom., cov: 32)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: PMP22 ENST00000674868.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 6 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: Ambry Genetics, Orphanet, Laboratory for Molecular Medicine, ClinGen, Labcorp Genetics (formerly Invitae)
• hereditary neuropathy with liability to pressure palsies

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

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000674868.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMP22	ENST00000674868.1		c.-592G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000502835.1	Q01453
	PMP22	ENST00000674868.1		c.-592G>T		5_prime_UTR	Exon 1 of 5	ENSP00000502835.1	Q01453
	PMP22	ENST00000431343.1	TSL:2	n.38G>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.322 AC: 49013 AN: 151980 Hom.: 8366 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.322

GnomAD4 exome AF: 0.333 AC: 4 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.333 AC XY: 4 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.300 AC: 3 AN: 10

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.322 AC: 49032 AN: 152098 Hom.: 8372 Cov.: 32 AF XY: 0.320 AC XY: 23791 AN XY: 74366

African (AFR) AF: 0.239 AC: 9932 AN: 41494

American (AMR) AF: 0.281 AC: 4302 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1129 AN: 3466

East Asian (EAS) AF: 0.115 AC: 597 AN: 5170

South Asian (SAS) AF: 0.372 AC: 1791 AN: 4816

European-Finnish (FIN) AF: 0.385 AC: 4070 AN: 10584

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26273 AN: 67972

Other (OTH) AF: 0.323 AC: 681 AN: 2108

Alfa AF: 0.358 Hom.: 33164

Bravo AF: 0.309

Asia WGS AF: 0.211 AC: 737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.56
PhyloP100		-0.14
PromoterAI		0.029	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8065610; hg19: chr17-15175570; COSMIC: COSV70800472;