16-4951379-A-G

Variant names:

• chr16-4951379-A-G
• rs9635542
• ENST00000592772.1:c.-92+9185T>C

Variant summary

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

The ENST00000592772.1(PPL):​c.-92+9185T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 151,542 control chromosomes in the GnomAD database, including 1,452 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 0.11 (1452 hom., cov: 30)
• Consequence: PPL ENST00000592772.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000592772.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPL	ENST00000592772.1	TSL:5	c.-92+9185T>C		intron	N/A	ENSP00000467699.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17347 AN: 151432 Hom.: 1448 Cov.: 30

Gnomad AFR AF: 0.0667

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0870

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.115 AC: 17367 AN: 151542 Hom.: 1452 Cov.: 30 AF XY: 0.121 AC XY: 8936 AN XY: 73984

African (AFR) AF: 0.0666 AC: 2752 AN: 41292

American (AMR) AF: 0.127 AC: 1934 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.0870 AC: 302 AN: 3470

East Asian (EAS) AF: 0.444 AC: 2270 AN: 5116

South Asian (SAS) AF: 0.274 AC: 1315 AN: 4804

European-Finnish (FIN) AF: 0.124 AC: 1291 AN: 10434

Middle Eastern (MID) AF: 0.117 AC: 34 AN: 290

European-Non Finnish (NFE) AF: 0.105 AC: 7140 AN: 67930

Other (OTH) AF: 0.119 AC: 250 AN: 2102

Alfa AF: 0.111 Hom.: 3838

Bravo AF: 0.110

Asia WGS AF: 0.376 AC: 1305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.50
PhyloP100		-0.61

Splicing

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

Other links and lift over

dbSNP: rs9635542; hg19: chr16-5001380;