ENST00000549190.5:c.34+42806C>A

Variant names:

• chr12-42281467-C-A
• rs2061192
• ENST00000965398.1:c.-21+42740C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000549190.5. 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.-21+42740C>A		intron	N/A	ENSP00000635457.1
	PPHLN1	ENST00000549190.5	TSL:5	c.34+42806C>A		intron	N/A	ENSP00000447168.1	F8W0Q9
	PPHLN1	ENST00000890820.1		c.-142-37182C>A		intron	N/A	ENSP00000560879.1

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

African (AFR) AF: 0.912 AC: 37916 AN: 41568

American (AMR) AF: 0.690 AC: 10539 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2228 AN: 3464

East Asian (EAS) AF: 0.831 AC: 4312 AN: 5188

South Asian (SAS) AF: 0.793 AC: 3827 AN: 4826

European-Finnish (FIN) AF: 0.615 AC: 6493 AN: 10556

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42974 AN: 68004

Other (OTH) AF: 0.719 AC: 1519 AN: 2112

Alfa AF: 0.663 Hom.: 18063

Bravo AF: 0.736

Asia WGS AF: 0.802 AC: 2786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.41
PhyloP100		-0.68
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: rs2061192; hg19: chr12-42675269;