chr16-4953073-C-A

Variant names:

• chr16-4953073-C-A
• rs34924084
• ENST00000592772.1:c.-92+7491G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.99).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPL	ENST00000592772.1	c.-92+7491G>T		intron_variant	Intron 1 of 9	5		ENSP00000467699.1

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

African (AFR) AF: 0.0135 AC: 539 AN: 40004

American (AMR) AF: 0.117 AC: 1707 AN: 14638

Ashkenazi Jewish (ASJ) AF: 0.0316 AC: 109 AN: 3452

East Asian (EAS) AF: 0.000421 AC: 2 AN: 4756

South Asian (SAS) AF: 0.0363 AC: 165 AN: 4550

European-Finnish (FIN) AF: 0.123 AC: 1220 AN: 9930

Middle Eastern (MID) AF: 0.0109 AC: 3 AN: 274

European-Non Finnish (NFE) AF: 0.0715 AC: 4816 AN: 67320

Other (OTH) AF: 0.0462 AC: 96 AN: 2078

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
PhyloP100		-3.7

Splicing

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

Other links and lift over

dbSNP: rs34924084; hg19: chr16-5003074;