rs2977310

Positions:

• chr1-17238495-T-C

Variant summary

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

The NM_013358.3(PADI1):​c.1459-121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 438,168 control chromosomes in the GnomAD database, including 54,210 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 0.51 (20463 hom., cov: 32)
  • Exomes 𝑓: 0.48 (33747 hom.)
• Consequence: PADI1 NM_013358.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

Genes affected

PADI1 (HGNC:18367): (peptidyl arginine deiminase 1) This gene encodes a member of the peptidyl arginine deiminase family of enzymes, which catalyze the post-translational deimination of proteins by converting arginine residues into citrullines in the presence of calcium ions. The family members have distinct substrate specificities and tissue-specific expression patterns. The type I enzyme is involved in the late stages of epidermal differentiation, where it deiminates filaggrin and keratin K1, which maintains hydration of the stratum corneum, and hence the cutaneous barrier function. This enzyme may also play a role in hair follicle formation. This gene exists in a cluster with four other paralogous genes. [provided by RefSeq, Jul 2008]

PADI1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI1	NM_013358.3	c.1459-121T>C		intron_variant		ENST00000375471.5	NP_037490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI1	ENST00000375471.5	c.1459-121T>C		intron_variant		1	NM_013358.3	ENSP00000364620.4

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78000 AN: 151844 Hom.: 20419 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.492

GnomAD4 exome AF: 0.481 AC: 137790 AN: 286206 Hom.: 33747 AF XY: 0.481 AC XY: 70541 AN XY: 146554

Gnomad4 AFR exome AF: 0.586

Gnomad4 AMR exome AF: 0.388

Gnomad4 ASJ exome AF: 0.443

Gnomad4 EAS exome AF: 0.392

Gnomad4 SAS exome AF: 0.543

Gnomad4 FIN exome AF: 0.460

Gnomad4 NFE exome AF: 0.494

Gnomad4 OTH exome AF: 0.497

GnomAD4 genome AF: 0.514 AC: 78096 AN: 151962 Hom.: 20463 Cov.: 32 AF XY: 0.513 AC XY: 38080 AN XY: 74282

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.498

Alfa AF: 0.497 Hom.: 24994

Bravo AF: 0.511

Asia WGS AF: 0.554 AC: 1928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.11
DANN	Benign	0.66

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: rs2977310; hg19: chr1-17564990; COSMIC: COSV64938775; COSMIC: COSV64938775;