rs12733102

Variant names:

• chr1-17336210-G-C
• rs12733102
• NM_012387.3:c.392G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_012387.3(PADI4):​c.392G>C​(p.Arg131Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 1,613,548 control chromosomes in the GnomAD database, including 452 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.016 (34 hom., cov: 33)
  • Exomes 𝑓: 0.022 (418 hom.)
• Consequence: PADI4 NM_012387.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• Publications: 15 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033593178).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.016 (2436/152282) while in subpopulation NFE AF = 0.0244 (1661/68030). AF 95% confidence interval is 0.0234. There are 34 homozygotes in GnomAd4. There are 1123 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 34 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	NM_012387.3	MANE Select	c.392G>C	p.Arg131Thr	missense	Exon 4 of 16	NP_036519.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	ENST00000375448.4	TSL:1 MANE Select	c.392G>C	p.Arg131Thr	missense	Exon 4 of 16	ENSP00000364597.4

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2432 AN: 152164 Hom.: 34 Cov.: 33

Gnomad AFR AF: 0.00437

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00910

Gnomad FIN AF: 0.0149

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0244

Gnomad OTH AF: 0.0215

GnomAD2 exomes AF: 0.0163 AC: 4087 AN: 251338 AF XY: 0.0168

Gnomad AFR exome AF: 0.00492

Gnomad AMR exome AF: 0.00926

Gnomad ASJ exome AF: 0.0206

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0170

Gnomad NFE exome AF: 0.0235

Gnomad OTH exome AF: 0.0204

GnomAD4 exome AF: 0.0218 AC: 31784 AN: 1461266 Hom.: 418 Cov.: 33 AF XY: 0.0216 AC XY: 15681 AN XY: 726990

African (AFR) AF: 0.00418 AC: 140 AN: 33468

American (AMR) AF: 0.00995 AC: 445 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 535 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00979 AC: 844 AN: 86250

European-Finnish (FIN) AF: 0.0175 AC: 934 AN: 53420

Middle Eastern (MID) AF: 0.0324 AC: 187 AN: 5768

European-Non Finnish (NFE) AF: 0.0246 AC: 27395 AN: 1111438

Other (OTH) AF: 0.0216 AC: 1303 AN: 60380

GnomAD4 genome AF: 0.0160 AC: 2436 AN: 152282 Hom.: 34 Cov.: 33 AF XY: 0.0151 AC XY: 1123 AN XY: 74450

African (AFR) AF: 0.00438 AC: 182 AN: 41556

American (AMR) AF: 0.0160 AC: 244 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00932 AC: 45 AN: 4830

European-Finnish (FIN) AF: 0.0149 AC: 158 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0244 AC: 1661 AN: 68030

Other (OTH) AF: 0.0222 AC: 47 AN: 2114

Alfa AF: 0.0234 Hom.: 41

Bravo AF: 0.0157

TwinsUK AF: 0.0248 AC: 92

ALSPAC AF: 0.0265 AC: 102

ESP6500AA AF: 0.00499 AC: 22

ESP6500EA AF: 0.0228 AC: 196

ExAC AF: 0.0160 AC: 1940

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.0261

EpiControl AF: 0.0272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.81
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.094	N
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.27
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.069
Sift	Benign	0.26	T
Sift4G	Benign	0.42	T
Polyphen		0.64	P
Vest4		0.062
MPC		0.30
ClinPred		0.011	T
GERP RS		-3.5
Varity_R		0.052
gMVP		0.14
Mutation Taster		=92/8	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: rs12733102; hg19: chr1-17662705;