rs2484067

Positions:

• chr6-138096278-T-C

Variant summary

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

The NM_022121.5(PERP):​c.355+76A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,531,570 control chromosomes in the GnomAD database, including 160,275 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 0.40 (13272 hom., cov: 32)
  • Exomes 𝑓: 0.45 (147003 hom.)
• Consequence: PERP NM_022121.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200

Genes affected

PERP (HGNC:17637): (p53 apoptosis effector related to PMP22) Involved in activation of cysteine-type endopeptidase activity. Predicted to be located in plasma membrane. Predicted to be active in cell-cell junction. Implicated in erythrokeratodermia variabilis and mutilating palmoplantar keratoderma with periorificial keratotic plaques. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PERP	NM_022121.5	c.355+76A>G		intron_variant		ENST00000421351.4	NP_071404.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PERP	ENST00000421351.4	c.355+76A>G		intron_variant		1	NM_022121.5	ENSP00000397157.2

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61416 AN: 151914 Hom.: 13264 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.0513

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.442

GnomAD4 exome AF: 0.452 AC: 623677 AN: 1379536 Hom.: 147003 AF XY: 0.450 AC XY: 307744 AN XY: 684260

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.542

Gnomad4 EAS exome AF: 0.0783

Gnomad4 SAS exome AF: 0.302

Gnomad4 FIN exome AF: 0.393

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.436

GnomAD4 genome AF: 0.404 AC: 61450 AN: 152034 Hom.: 13272 Cov.: 32 AF XY: 0.394 AC XY: 29315 AN XY: 74330

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.0516

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.438

Alfa AF: 0.467 Hom.: 18427

Bravo AF: 0.400

Asia WGS AF: 0.195 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
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: rs2484067; hg19: chr6-138417415; COSMIC: COSV69827760;