rs8065610

chr17-15272253-C-Achr17-15272253-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000654786.1(ENSG00000286792):n.137+5269C>A variant causes a intron, non coding transcript 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: ENST00000654786.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

Genes affected

(HGNC:):

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]

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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000654786.1	n.137+5269C>A		intron_variant, non_coding_transcript_variant
PMP22	ENST00000674868.1	c.-592G>T		5_prime_UTR_variant	1/5			P1
PMP22	ENST00000431343.1	n.38G>T		non_coding_transcript_exon_variant	1/2	2
PMP22	ENST00000676194.1	n.29G>T		non_coding_transcript_exon_variant	1/1

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;