rs34924084

Positions:

• chr16-4953073-C-A
• chr16-4953073-C-T

Variant summary

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

The ENST00000592772.1(PPL):​c.-92+7491G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0591 in 147,906 control chromosomes in the GnomAD database, including 397 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 0.059 (397 hom., cov: 27)
• Consequence: PPL ENST00000592772.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.67

Genes affected

PPL (HGNC:9273): (periplakin) The protein encoded by this gene is a component of desmosomes and of the epidermal cornified envelope in keratinocytes. The N-terminal domain of this protein interacts with the plasma membrane and its C-terminus interacts with intermediate filaments. Through its rod domain, this protein forms complexes with envoplakin. This protein may serve as a link between the cornified envelope and desmosomes as well as intermediate filaments. AKT1/PKB, a protein kinase mediating a variety of cell growth and survival signaling processes, is reported to interact with this protein, suggesting a possible role for this protein as a localization signal in AKT1-mediated signaling. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPL	ENST00000592772.1	c.-92+7491G>T		intron_variant		5		ENSP00000467699

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 8739 AN: 147798 Hom.: 397 Cov.: 27

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.0918

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0316

Gnomad EAS AF: 0.000420

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0101

Gnomad NFE AF: 0.0715

Gnomad OTH AF: 0.0466

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0591 AC: 8740 AN: 147906 Hom.: 397 Cov.: 27 AF XY: 0.0618 AC XY: 4444 AN XY: 71946

Gnomad4 AFR AF: 0.0135

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.0316

Gnomad4 EAS AF: 0.000421

Gnomad4 SAS AF: 0.0363

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0715

Gnomad4 OTH AF: 0.0462

Alfa AF: 0.0311 Hom.: 28

Bravo AF: 0.0545

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.27
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34924084; hg19: chr16-5003074;