rs1621005

Positions:

• chr1-17336256-C-G

Variant summary

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

The NM_012387.3(PADI4):​c.408+30C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,587,572 control chromosomes in the GnomAD database, including 349,626 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 0.64 (31665 hom., cov: 33)
  • Exomes 𝑓: 0.66 (317961 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

Genes affected

PADI4 (HGNC:18368): (peptidyl arginine deiminase 4) This gene is a member of a gene family which encodes enzymes responsible for the conversion of arginine residues to citrulline residues. This gene may play a role in granulocyte and macrophage development leading to inflammation and immune response. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3	c.408+30C>G		intron_variant		ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4	c.408+30C>G		intron_variant		1	NM_012387.3	P1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97787 AN: 152028 Hom.: 31656 Cov.: 33

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.607

GnomAD3 exomes AF: 0.634 AC: 157977 AN: 249002 Hom.: 50678 AF XY: 0.637 AC XY: 85732 AN XY: 134558

Gnomad AFR exome AF: 0.601

Gnomad AMR exome AF: 0.534

Gnomad ASJ exome AF: 0.654

Gnomad EAS exome AF: 0.628

Gnomad SAS exome AF: 0.573

Gnomad FIN exome AF: 0.680

Gnomad NFE exome AF: 0.677

Gnomad OTH exome AF: 0.638

GnomAD4 exome AF: 0.664 AC: 952515 AN: 1435426 Hom.: 317961 Cov.: 26 AF XY: 0.662 AC XY: 473576 AN XY: 715640

Gnomad4 AFR exome AF: 0.597

Gnomad4 AMR exome AF: 0.546

Gnomad4 ASJ exome AF: 0.662

Gnomad4 EAS exome AF: 0.642

Gnomad4 SAS exome AF: 0.578

Gnomad4 FIN exome AF: 0.677

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.644

GnomAD4 genome AF: 0.643 AC: 97835 AN: 152146 Hom.: 31665 Cov.: 33 AF XY: 0.643 AC XY: 47819 AN XY: 74374

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.599

Alfa AF: 0.659 Hom.: 6098

Bravo AF: 0.633

Asia WGS AF: 0.569 AC: 1977 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.1
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1621005; hg19: chr1-17662751; COSMIC: COSV64923483; COSMIC: COSV64923483;