rs116975820

Positions:

• chr12-42329106-T-G

Variant summary

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

The NM_201439.2(PPHLN1):​c.-21+2877T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 139,238 control chromosomes in the GnomAD database, including 985 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 0.12 (985 hom., cov: 29)
• Consequence: PPHLN1 NM_201439.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282

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]

PPHLN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPHLN1	NM_201439.2	c.-21+2877T>G		intron_variant		ENST00000358314.12	NP_958847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPHLN1	ENST00000358314.12	c.-21+2877T>G		intron_variant		2	NM_201439.2	ENSP00000351066.7

Frequencies

GnomAD3 genomes AF: 0.120 AC: 16643 AN: 139144 Hom.: 984 Cov.: 29

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.0985

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0672

Gnomad SAS AF: 0.0868

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0795

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.120 AC: 16642 AN: 139238 Hom.: 985 Cov.: 29 AF XY: 0.119 AC XY: 8101 AN XY: 67942

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0982

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.0668

Gnomad4 SAS AF: 0.0871

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.111

Alfa AF: 0.110 Hom.: 75

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs116975820; hg19: chr12-42722908;