1-17363459-C-T

Position:

• chr1-17363459-C-T

Variant summary

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

The NM_012387.3(PADI4):​c.1759-63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,133,392 control chromosomes in the GnomAD database, including 32,018 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 0.23 (4138 hom., cov: 32)
  • Exomes 𝑓: 0.23 (27880 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI4	NM_012387.3	c.1759-63C>T		intron_variant		ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.1759-63C>T		intron_variant		1	NM_012387.3	ENSP00000364597.4

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34937 AN: 151930 Hom.: 4134 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.240

GnomAD4 exome AF: 0.234 AC: 229819 AN: 981344 Hom.: 27880 AF XY: 0.234 AC XY: 117211 AN XY: 501578

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.309

Gnomad4 EAS exome AF: 0.289

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.242

GnomAD4 genome AF: 0.230 AC: 34966 AN: 152048 Hom.: 4138 Cov.: 32 AF XY: 0.226 AC XY: 16798 AN XY: 74330

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.238

Alfa AF: 0.238 Hom.: 500

Bravo AF: 0.233

Asia WGS AF: 0.232 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.47

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: rs2477150; hg19: chr1-17689954; COSMIC: COSV64924128; COSMIC: COSV64924128;