rs11181399

chr12-42272610-G-A

Variant summary

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

The ENST00000549190.5(PPHLN1):c.34+33949G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,136 control chromosomes in the GnomAD database, including 11,142 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 (11142 hom., cov: 33)
• Consequence: PPHLN1 ENST00000549190.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPHLN1	ENST00000549190.5	c.34+33949G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57593 AN: 152018 Hom.: 11134 Cov.: 33

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.379 AC: 57637 AN: 152136 Hom.: 11142 Cov.: 33 AF XY: 0.385 AC XY: 28612 AN XY: 74372

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.364

Alfa AF: 0.381 Hom.: 1386

Bravo AF: 0.361

Asia WGS AF: 0.429 AC: 1488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.8
Dann	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11181399; hg19: chr12-42666412;