chr16-4882559-T-G

Variant names:

• chr16-4882559-T-G
• rs7214
• NM_002705.5:c.*825A>C

Variant summary

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

The NM_002705.5(PPL):​c.*825A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,892 control chromosomes in the GnomAD database, including 23,657 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 0.53 (23655 hom., cov: 31)
  • Exomes 𝑓: 0.16 (2 hom.)
• Consequence: PPL NM_002705.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469
• Publications: 16 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]

UBN1 (HGNC:12506): (ubinuclein 1) Cellular senescence is a hallmark of tumor suppression and tissue aging. Senescent cells contain domains of heterochromatin, called senescence-associated heterochromatin foci (SAHF), that repress proliferation-promoting genes. The protein encoded by this gene binds to proliferation-promoting genes and is required for SAHF formation, enhancing methylation of histone H3. [provided by RefSeq, Oct 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002705.5. 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
	PPL	NM_002705.5	MANE Select	c.*825A>C		3_prime_UTR	Exon 22 of 22	NP_002696.4
	UBN1	NM_001079514.3	MANE Select	c.*2427T>G		downstream_gene	N/A	NP_001072982.1
	UBN1	NM_001288656.1		c.*2427T>G		downstream_gene	N/A	NP_001275585.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPL	ENST00000345988.7	TSL:1 MANE Select	c.*825A>C		3_prime_UTR	Exon 22 of 22	ENSP00000340510.2
	UBN1	ENST00000262376.11	TSL:1 MANE Select	c.*2427T>G		downstream_gene	N/A	ENSP00000262376.5
	UBN1	ENST00000396658.8	TSL:1	c.*2427T>G		downstream_gene	N/A	ENSP00000379894.3

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80891 AN: 151712 Hom.: 23603 Cov.: 31

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.517

GnomAD4 exome AF: 0.161 AC: 10 AN: 62 Hom.: 2 Cov.: 0 AF XY: 0.158 AC XY: 6 AN XY: 38

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0800 AC: 4 AN: 50

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.400 AC: 4 AN: 10

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.533 AC: 80998 AN: 151830 Hom.: 23655 Cov.: 31 AF XY: 0.530 AC XY: 39323 AN XY: 74186

African (AFR) AF: 0.784 AC: 32440 AN: 41374

American (AMR) AF: 0.490 AC: 7471 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1831 AN: 3466

East Asian (EAS) AF: 0.355 AC: 1827 AN: 5152

South Asian (SAS) AF: 0.536 AC: 2581 AN: 4812

European-Finnish (FIN) AF: 0.383 AC: 4033 AN: 10530

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29283 AN: 67928

Other (OTH) AF: 0.521 AC: 1095 AN: 2102

Alfa AF: 0.480 Hom.: 11143

Bravo AF: 0.556

Asia WGS AF: 0.518 AC: 1801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.7
DANN	Benign	0.69
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7214; hg19: chr16-4932560;