rs2240335

chr1-17348042-C-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_012387.3(PADI4):c.1149C>A(p.Arg383=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,587,424 control chromosomes in the GnomAD database, including 107,661 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (10786 hom., cov: 31)
  • Exomes 𝑓: 0.36 (96875 hom.)
• Consequence: PADI4 NM_012387.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.32

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 1-17348042-C-A is Benign according to our data. Variant chr1-17348042-C-A is described in ClinVar as [Benign]. Clinvar id is 3059475.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.32 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3	c.1149C>A	p.Arg383=	synonymous_variant	10/16	ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4	c.1149C>A	p.Arg383=	synonymous_variant	10/16	1	NM_012387.3	P1
PADI4	ENST00000468945.1	n.208C>A		non_coding_transcript_exon_variant	2/2	2
PADI4	ENST00000487048.5	n.116C>A		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56417 AN: 151764 Hom.: 10789 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.364

GnomAD3 exomes AF: 0.389 AC: 97177 AN: 249762 Hom.: 19741 AF XY: 0.391 AC XY: 52813 AN XY: 135028

Gnomad AFR exome AF: 0.373

Gnomad AMR exome AF: 0.410

Gnomad ASJ exome AF: 0.415

Gnomad EAS exome AF: 0.583

Gnomad SAS exome AF: 0.436

Gnomad FIN exome AF: 0.335

Gnomad NFE exome AF: 0.349

Gnomad OTH exome AF: 0.383

GnomAD4 exome AF: 0.363 AC: 520593 AN: 1435542 Hom.: 96875 Cov.: 26 AF XY: 0.365 AC XY: 261546 AN XY: 715620

Gnomad4 AFR exome AF: 0.370

Gnomad4 AMR exome AF: 0.418

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.584

Gnomad4 SAS exome AF: 0.439

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.372

GnomAD4 genome AF: 0.372 AC: 56442 AN: 151882 Hom.: 10786 Cov.: 31 AF XY: 0.375 AC XY: 27827 AN XY: 74216

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.359

Alfa AF: 0.363 Hom.: 17472

Bravo AF: 0.380

Asia WGS AF: 0.441 AC: 1529 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PADI4-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	1.0
Dann	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2240335; hg19: chr1-17674537; COSMIC: COSV64923856; COSMIC: COSV64923856;