rs35903413

Variant names:

• chr1-17342068-G-A
• rs35903413
• NM_012387.3:c.778G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_012387.3(PADI4):​c.778G>A​(p.Asp260Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,613,568 control chromosomes in the GnomAD database, including 13,423 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.096 (962 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12461 hom.)
• Consequence: PADI4 NM_012387.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.621
• Publications: 20 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002902478).
• BP6: Variant 1-17342068-G-A is Benign according to our data. Variant chr1-17342068-G-A is described in ClinVar as Benign. ClinVar VariationId is 3056879.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012387.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	NM_012387.3	MANE Select	c.778G>A	p.Asp260Asn	missense	Exon 7 of 16	NP_036519.2	Q9UM07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	ENST00000375448.4	TSL:1 MANE Select	c.778G>A	p.Asp260Asn	missense	Exon 7 of 16	ENSP00000364597.4	Q9UM07

Frequencies

GnomAD3 genomes AF: 0.0964 AC: 14667 AN: 152072 Hom.: 963 Cov.: 32

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.0790

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0446

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.0955

GnomAD2 exomes AF: 0.101 AC: 25341 AN: 251420 AF XY: 0.103

Gnomad AFR exome AF: 0.0272

Gnomad AMR exome AF: 0.0501

Gnomad ASJ exome AF: 0.0843

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.123 AC: 179573 AN: 1461378 Hom.: 12461 Cov.: 32 AF XY: 0.122 AC XY: 88451 AN XY: 727034

African (AFR) AF: 0.0252 AC: 845 AN: 33476

American (AMR) AF: 0.0523 AC: 2338 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0852 AC: 2225 AN: 26130

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39700

South Asian (SAS) AF: 0.0474 AC: 4087 AN: 86254

European-Finnish (FIN) AF: 0.167 AC: 8926 AN: 53418

Middle Eastern (MID) AF: 0.0964 AC: 554 AN: 5748

European-Non Finnish (NFE) AF: 0.139 AC: 154300 AN: 1111550

Other (OTH) AF: 0.104 AC: 6290 AN: 60380

GnomAD4 genome AF: 0.0963 AC: 14662 AN: 152190 Hom.: 962 Cov.: 32 AF XY: 0.0960 AC XY: 7144 AN XY: 74396

African (AFR) AF: 0.0297 AC: 1234 AN: 41550

American (AMR) AF: 0.0789 AC: 1206 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 301 AN: 3472

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.0445 AC: 214 AN: 4812

European-Finnish (FIN) AF: 0.167 AC: 1769 AN: 10600

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9420 AN: 67990

Other (OTH) AF: 0.0945 AC: 199 AN: 2106

Alfa AF: 0.115 Hom.: 2666

Bravo AF: 0.0848

TwinsUK AF: 0.134 AC: 496

ALSPAC AF: 0.139 AC: 535

ESP6500AA AF: 0.0297 AC: 131

ESP6500EA AF: 0.129 AC: 1107

ExAC AF: 0.103 AC: 12476

Asia WGS AF: 0.0250 AC: 89 AN: 3478

EpiCase AF: 0.132

EpiControl AF: 0.136

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PADI4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.1
DANN	Benign	0.89
DEOGEN2	Benign	0.042	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.010	N
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.62
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.018
Sift	Benign	0.35	T
Sift4G	Benign	0.17	T
Polyphen		0.011	B
Vest4		0.014
MPC		0.11
ClinPred		0.00080	T
GERP RS		1.3
Varity_R		0.092
gMVP		0.20
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35903413; hg19: chr1-17668563; COSMIC: COSV64923853; COSMIC: COSV64923853;