rs2240335

Variant names:

• chr1-17348042-C-A
• rs2240335
• NM_012387.3:c.1149C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-17348042-C-A
• chr1-17348042-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_012387.3(PADI4):​c.1149C>A​(p.Arg383Arg) 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.37 (10786 hom., cov: 31)
  • Exomes 𝑓: 0.36 (96875 hom.)
• Consequence: PADI4 NM_012387.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.32
• Publications: 77 publications found

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

Our verdict: Benign. The variant received -14 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 VariationId is 3059475.Status of the report is no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.1149C>A	p.Arg383Arg	synonymous_variant	Exon 10 of 16	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.1149C>A	p.Arg383Arg	synonymous_variant	Exon 10 of 16	1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000468945.1	n.208C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
PADI4	ENST00000487048.5	n.116C>A		non_coding_transcript_exon_variant	Exon 1 of 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

GnomAD2 exomes AF: 0.389 AC: 97177 AN: 249762 AF XY: 0.391

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 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

African (AFR) AF: 0.370 AC: 12193 AN: 32954

American (AMR) AF: 0.418 AC: 18568 AN: 44472

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 10790 AN: 25860

East Asian (EAS) AF: 0.584 AC: 23079 AN: 39518

South Asian (SAS) AF: 0.439 AC: 37456 AN: 85302

European-Finnish (FIN) AF: 0.333 AC: 17721 AN: 53238

Middle Eastern (MID) AF: 0.402 AC: 2294 AN: 5708

European-Non Finnish (NFE) AF: 0.346 AC: 376399 AN: 1089036

Other (OTH) AF: 0.372 AC: 22093 AN: 59454

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

African (AFR) AF: 0.367 AC: 15211 AN: 41420

American (AMR) AF: 0.418 AC: 6389 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1465 AN: 3464

East Asian (EAS) AF: 0.589 AC: 3017 AN: 5118

South Asian (SAS) AF: 0.451 AC: 2172 AN: 4812

European-Finnish (FIN) AF: 0.333 AC: 3515 AN: 10548

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23606 AN: 67928

Other (OTH) AF: 0.359 AC: 758 AN: 2110

Alfa AF: 0.362 Hom.: 40821

Bravo AF: 0.380

Asia WGS AF: 0.441 AC: 1529 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PADI4-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2240335; hg19: chr1-17674537; COSMIC: COSV64923856; COSMIC: COSV64923856;