rs7954523

chr12-42287706-A-G

Variant summary

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

The ENST00000550858.1(ENSG00000257674):n.796A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,036,922 control chromosomes in the GnomAD database, including 81,363 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 (11105 hom., cov: 34)
  • Exomes 𝑓: 0.39 (70258 hom.)
• Consequence: ENST00000550858.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

Genes affected

(HGNC:):

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=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.462 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
	ENST00000550858.1	n.796A>G		non_coding_transcript_exon_variant	1/1
PPHLN1	ENST00000549190.5	c.35-48177A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57461 AN: 152064 Hom.: 11098 Cov.: 34

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.365

GnomAD4 exome AF: 0.395 AC: 349340 AN: 884740 Hom.: 70258 Cov.: 13 AF XY: 0.400 AC XY: 185300 AN XY: 463284

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.280

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.414

Gnomad4 SAS exome AF: 0.484

Gnomad4 FIN exome AF: 0.449

Gnomad4 NFE exome AF: 0.391

Gnomad4 OTH exome AF: 0.389

GnomAD4 genome AF: 0.378 AC: 57499 AN: 152182 Hom.: 11105 Cov.: 34 AF XY: 0.384 AC XY: 28557 AN XY: 74400

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.364

Alfa AF: 0.386 Hom.: 2451

Bravo AF: 0.360

Asia WGS AF: 0.428 AC: 1483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	7.7
Dann	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7954523; hg19: chr12-42681508; COSMIC: COSV73527160;