rs34481461

chr1-17358971-C-A

Variant summary

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

The NM_012387.3(PADI4):c.1629+63C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,138,122 control chromosomes in the GnomAD database, including 17,041 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 0.14 (1780 hom., cov: 31)
  • Exomes 𝑓: 0.17 (15261 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3	c.1629+63C>A		intron_variant		ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4	c.1629+63C>A		intron_variant		1	NM_012387.3	P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21142 AN: 152084 Hom.: 1786 Cov.: 31

Gnomad AFR AF: 0.0618

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.169 AC: 166277 AN: 985918 Hom.: 15261 AF XY: 0.171 AC XY: 86169 AN XY: 504190

Gnomad4 AFR exome AF: 0.0552

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.302

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.139 AC: 21135 AN: 152204 Hom.: 1780 Cov.: 31 AF XY: 0.136 AC XY: 10118 AN XY: 74418

Gnomad4 AFR AF: 0.0618

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.173

Alfa AF: 0.149 Hom.: 214

Bravo AF: 0.141

Asia WGS AF: 0.204 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.1
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs34481461; hg19: chr1-17685466; COSMIC: COSV64923279; COSMIC: COSV64923279;