rs12371762

Positions:

• chr12-42288549-C-T

Variant summary

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

The ENST00000549190.5(PPHLN1):​c.35-47334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,602,254 control chromosomes in the GnomAD database, including 129,101 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 0.35 (9776 hom., cov: 32)
  • Exomes 𝑓: 0.40 (119325 hom.)
• Consequence: PPHLN1 ENST00000549190.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.47

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC727884		n.42288549C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPHLN1	ENST00000549190.5	c.35-47334C>T		intron_variant		5		ENSP00000447168.1
ENSG00000257674	ENST00000550858.1	n.1639C>T		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52703 AN: 151902 Hom.: 9773 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.402 AC: 582567 AN: 1450234 Hom.: 119325 Cov.: 32 AF XY: 0.405 AC XY: 292555 AN XY: 721960

Gnomad4 AFR exome AF: 0.211

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.416

Gnomad4 SAS exome AF: 0.488

Gnomad4 FIN exome AF: 0.449

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.392

GnomAD4 genome AF: 0.347 AC: 52726 AN: 152020 Hom.: 9776 Cov.: 32 AF XY: 0.354 AC XY: 26267 AN XY: 74304

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.343

Alfa AF: 0.375 Hom.: 3214

Bravo AF: 0.324

Asia WGS AF: 0.424 AC: 1470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12371762; hg19: chr12-42682351;