rs2301888

Positions:

• chr1-17346235-G-A

Variant summary

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

The NM_012387.3(PADI4):​c.1047+96G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 704,740 control chromosomes in the GnomAD database, including 47,023 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 0.32 (8441 hom., cov: 31)
  • Exomes 𝑓: 0.36 (38582 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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 = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3	c.1047+96G>A		intron_variant		ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4	c.1047+96G>A		intron_variant		1	NM_012387.3	P1
PADI4	ENST00000468945.1	n.106+96G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48116 AN: 151850 Hom.: 8451 Cov.: 31

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.364 AC: 201481 AN: 552772 Hom.: 38582 AF XY: 0.368 AC XY: 108548 AN XY: 294726

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.396

Gnomad4 ASJ exome AF: 0.405

Gnomad4 EAS exome AF: 0.578

Gnomad4 SAS exome AF: 0.429

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.359

GnomAD4 genome AF: 0.316 AC: 48096 AN: 151968 Hom.: 8441 Cov.: 31 AF XY: 0.323 AC XY: 23970 AN XY: 74298

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.324

Alfa AF: 0.356 Hom.: 6564

Bravo AF: 0.318

Asia WGS AF: 0.421 AC: 1462 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	6.5
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2301888; hg19: chr1-17672730;