rs2061192

Positions:

• chr12-42281467-C-A

Variant summary

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

The ENST00000549190.5(PPHLN1):​c.34+42806C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,200 control chromosomes in the GnomAD database, including 41,414 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 0.73 (41414 hom., cov: 34)
• Consequence: PPHLN1 ENST00000549190.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.678

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.42281467C>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPHLN1	ENST00000549190.5	c.34+42806C>A		intron_variant		5		ENSP00000447168.1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110459 AN: 152080 Hom.: 41365 Cov.: 34

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.718

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

GnomAD4 genome AF: 0.726 AC: 110568 AN: 152200 Hom.: 41414 Cov.: 34 AF XY: 0.728 AC XY: 54132 AN XY: 74386

Gnomad4 AFR AF: 0.912

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.793

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.719

Alfa AF: 0.663 Hom.: 16146

Bravo AF: 0.736

Asia WGS AF: 0.802 AC: 2786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2061192; hg19: chr12-42675269;