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. Variant got -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

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]

ENSG00000286792 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMP22	ENST00000674868.1	c.-592G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5			ENSP00000502835.1
PMP22	ENST00000674868.1	c.-592G>T		5_prime_UTR_variant	Exon 1 of 5			ENSP00000502835.1
PMP22	ENST00000431343.1	n.38G>T		non_coding_transcript_exon_variant	Exon 1 of 2	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

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.323

Alfa AF: 0.361 Hom.: 14557

Bravo AF: 0.309

Asia WGS AF: 0.211 AC: 737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

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