rs7954523

Variant names:

• chr12-42287706-A-G
• rs7954523
• ENST00000965398.1:c.-20-48177A>G

Variant summary

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

The ENST00000965398.1(PPHLN1):​c.-20-48177A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,036,922 control chromosomes in the GnomAD database, including 81,363 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 0.38 (11105 hom., cov: 34)
  • Exomes 𝑓: 0.39 (70258 hom.)
• Consequence: PPHLN1 ENST00000965398.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97
• Publications: 7 publications found

Genes affected

PPHLN1 (HGNC:19369): (periphilin 1) The protein encoded by this gene is one of the several proteins that become sequentially incorporated into the cornified cell envelope during the terminal differentiation of keratinocyte at the outer layers of epidermis. This protein interacts with periplakin, which is known as a precursor of the cornified cell envelope. The cellular localization pattern and insolubility of this protein suggest that it may play a role in epithelial differentiation and contribute to epidermal integrity and barrier formation. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ENSG00000257674 (HGNC:58593):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000965398.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPHLN1	ENST00000965398.1		c.-20-48177A>G		intron	N/A	ENSP00000635457.1
	PPHLN1	ENST00000549190.5	TSL:5	c.35-48177A>G		intron	N/A	ENSP00000447168.1	F8W0Q9
	PPHLN1	ENST00000890820.1		c.-142-30943A>G		intron	N/A	ENSP00000560879.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57461 AN: 152064 Hom.: 11098 Cov.: 34

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.365

GnomAD4 exome AF: 0.395 AC: 349340 AN: 884740 Hom.: 70258 Cov.: 13 AF XY: 0.400 AC XY: 185300 AN XY: 463284

African (AFR) AF: 0.321 AC: 7274 AN: 22694

American (AMR) AF: 0.280 AC: 12316 AN: 44040

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 7811 AN: 22624

East Asian (EAS) AF: 0.414 AC: 15379 AN: 37112

South Asian (SAS) AF: 0.484 AC: 36019 AN: 74432

European-Finnish (FIN) AF: 0.449 AC: 23891 AN: 53224

Middle Eastern (MID) AF: 0.388 AC: 1180 AN: 3038

European-Non Finnish (NFE) AF: 0.391 AC: 229483 AN: 586466

Other (OTH) AF: 0.389 AC: 15987 AN: 41110

GnomAD4 genome AF: 0.378 AC: 57499 AN: 152182 Hom.: 11105 Cov.: 34 AF XY: 0.384 AC XY: 28557 AN XY: 74400

African (AFR) AF: 0.329 AC: 13640 AN: 41512

American (AMR) AF: 0.320 AC: 4900 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1179 AN: 3466

East Asian (EAS) AF: 0.418 AC: 2162 AN: 5174

South Asian (SAS) AF: 0.479 AC: 2312 AN: 4830

European-Finnish (FIN) AF: 0.459 AC: 4854 AN: 10586

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27126 AN: 68004

Other (OTH) AF: 0.364 AC: 769 AN: 2112

Alfa AF: 0.385 Hom.: 2496

Bravo AF: 0.360

Asia WGS AF: 0.428 AC: 1483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.7
DANN	Benign	0.80
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7954523; hg19: chr12-42681508; COSMIC: COSV73527160;